| 1. |
- Ahlin, Sofie, 1985, et al.
(author)
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Adipose Tissue-Derived Human Serum Amyloid A Does Not Affect Atherosclerotic Lesion Area in hSAA(+/) (-/)ApoE(-/-) Mice
- 2014
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Journal article (peer-reviewed)abstract
- Chronically elevated serum levels of serum amyloid A (SAA) are linked to increased risk of cardiovascular disease. However, whether SAA is directly involved in atherosclerosis development is still not known. The aim of this study was to investigate the effects of adipose tissue-derived human SAA on atherosclerosis in mice. hSAA1(+/-) transgenic mice (hSAA1 mice) with a specific expression of human SAA1 in adipose tissue were bred with ApoE-deficient mice. The hSAA1 mice and their wild type (wt) littermates were fed normal chow for 35 weeks. At the end of the experiment, the mice were euthanized and blood, gonadal adipose tissue and aortas were collected. Plasma levels of SAA, cholesterol and triglycerides were measured. Atherosclerotic lesion areas were analyzed in the aortic arch, the thoracic aorta and the abdominal aorta in en face preparations of aorta stained with Sudan IV. The human SAA protein was present in plasma from hSAA1 mice but undetectable in wt mice. Similar plasma levels of cholesterol and triglycerides were observed in hSAA1 mice and their wt controls. There were no differences in atherosclerotic lesion areas in any sections of the aorta in hSAA1 mice compared to wt mice. In conclusion, our data suggest that adipose tissue-derived human SAA does not influence atherosclerosis development in mice.
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| 2. |
- Ahlin, Sofie, 1985, et al.
(author)
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Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study
- 2020
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
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Journal article (peer-reviewed)abstract
- Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
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| 3. |
- Ahlin, Sofie, 1985, et al.
(author)
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Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity.
- 2013
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In: Obesity (Silver Spring, Md.). - : Wiley. - 1930-739X .- 1930-7381. ; 21:12
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Journal article (peer-reviewed)abstract
- Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
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| 4. |
- Ahlin, Sofie, 1985, et al.
(author)
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No Evidence for a Role of Adipose Tissue-Derived Serum Amyloid A in the Development of Insulin Resistance or Obesity-Related Inflammation in hSAA1(+/)- Transgenic Mice
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
-
Journal article (peer-reviewed)abstract
- Obesity is associated with a low-grade inflammation including moderately increased serum levels of the acute phase protein serum amyloid A (SAA). In obesity, SAA is mainly produced from adipose tissue and serum levels of SAA are associated with insulin resistance. SAA has been described as a chemoattractant for inflammatory cells and adipose tissue from obese individuals contains increased numbers of macrophages. However, whether adipose tissue-derived SAA can have a direct impact on macrophage infiltration in adipose tissue or the development of insulin resistance is unknown. The aim of this study was to investigate the effects of adipose tissue-derived SAA1 on the development of insulin resistance and obesity-related inflammation. We have previously established a transgenic mouse model expressing human SAA1 in the adipose tissue. For this report, hSAA1(+/-) transgenic mice and wild type mice were fed with a high fat diet or normal chow. Effects of hSAA1 on glucose metabolism were assessed using an oral glucose tolerance test. Real-time PCR was used to measure the mRNA levels of macrophage markers and genes related to insulin sensitivity in adipose tissue. Cytokines during inflammation were analyzed using a Proinflammatory 7-plex Assay. We found similar insulin and glucose levels in hSAA1 mice and wt controls during an oral glucose tolerance test and no decrease in mRNA levels of genes related to insulin sensitivity in adipose tissue in neither male nor female hSAA1 animals. Furthermore, serum levels of proinflammatory cytokines and mRNA levels of macrophage markers in adipose tissue were not increased in hSAA1 mice. Hence, in this model we find no evidence that adipose tissue-derived hSAA1 influences the development of insulin resistance or obesity-related inflammation.
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| 5. |
- Andersson-Assarsson, Johanna C., 1974, et al.
(author)
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Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity
- 2023
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In: Ebiomedicine. - 2352-3964. ; 92
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Journal article (peer-reviewed)abstract
- Background Haematopoietic clones caused by somatic mutations with >= 2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years.Methods Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care.Findings In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04).Interpretation Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care.
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| 6. |
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| 7. |
- Anveden, Åsa, et al.
(author)
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Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study
- 2017
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 145:2, s. 224-229
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Journal article (peer-reviewed)abstract
- Objective. To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. Methods. The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 3760 years and BMI was >= 38 kg/m(2). Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1 years (interquartile range 14.8-20.9 years, maximum 26 years). This study is registered with ClinicalTrials.gov, NCT01479452. Results. Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio = 0.71; 95% CI 0.59-0.85; p < 0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio = 0.68; 95% CI 0.52-0.88; p = 0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value = 0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio = 0.56: 95% CI 035-0.89; p = 0.014). Conclusions. In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline.
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| 8. |
- Bruze, Gustaf, et al.
(author)
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Associations of Bariatric Surgery With Changes in Interpersonal Relationship Status Results From 2 Swedish Cohort Studies
- 2018
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In: JAMA Surgery. - : American Medical Association. - 2168-6254 .- 2168-6262. ; 153:7, s. 654-661
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Journal article (peer-reviewed)abstract
- IMPORTANCE: Bariatric surgery is a life-changing treatment for patients with severe obesity, but little is known about its association with interpersonal relationships.OBJECTIVES: To investigate if relationship status is altered after bariatric surgery.DESIGN, SETTING, AND PARTICIPANTS: Changes in relationship status after bariatric surgery were examined in 2 cohorts: (1) the prospective Swedish Obese Subjects (SOS) study, which recruited patients undergoing bariatric surgery from September 1, 1987, to January 31, 2001, and compared their care with usual nonsurgical care in matched obese control participants; and (2) participants from the Scandinavian Obesity Surgery Registry (SOReg), a prospective, electronically captured register that recruited patients from January 2007 through December 2012 and selected comparator participants from the general population matched on age, sex, and place of residence. Data was collected in surgical departments and primary health care centers in Sweden. The current analysis includes data collected up until July 2015 (SOS) and December 2012 (SOReg). Data analysis was completed from June 2016 to December 2017.MAIN OUTCOMES AND MEASURES: In the SOS study, information on relationship status was obtained from questionnaires. In the SOReg and general population cohort, information on marriage and divorce was obtained from the Swedish Total Population Registry.RESULTS: The SOS study included 1958 patients who had bariatric surgery (of whom 1389 [70.9%] were female) and 1912 matched obese controls (of whom 1354 [70.8%] were female) and had a median (range) follow-up of 10 (0.5-20) years. The SOReg cohort included 29 234 patients who had gastric bypass surgery (of whom 22 131 [75.6%] were female) and 283 748 comparators from the general population (of whom 214 342 [75.5%] were female), and had a median (range) follow-up of 2.9 (0.003-7.0) years. In the SOS study, the surgical patients received gastric banding (n = 368; 18.8%), vertical banded gastroplasty (n = 1331; 68.0%), or gastric bypass (n = 259; 13.2%); controls received usual obesity care. In SOReg, all 29 234 surgical participants received gastric bypass surgery. In the SOS study, bariatric surgery was associated with increased incidence of divorce/separation compared with controls for those in a relationship (adjusted hazard ratio [aHR] = 1.28; 95% CI, 1.03-1.60; P =.03) and increased incidence of marriage or new relationship (aHR = 2.03; 95% CI, 1.52-2.71; P <.001) in those who were unmarried or single at baseline. In the SOReg and general population cohort, gastric bypass was associated with increased incidence of divorce compared with married control participants (aHR = 1.41; 95% CI, 1.33-1.49; P <.001) and increased incidence of marriage in those who were unmarried at baseline (aHR = 1.35; 95% CI, 1.28-1.42; P <.001). Within the surgery groups, changes in relationship status were more common in those with larger weight loss.CONCLUSIONS AND RELEVANCE: In addition to its association with obesity comorbidities, bariatric surgery-induced weight loss is also associated with changes in relationship status.
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| 9. |
- Burza, Maria Antonella, 1980, et al.
(author)
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Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3
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Journal article (peer-reviewed)abstract
- Background and Aim: Obesity is associated with elevated serum transaminase levels and non- Methods: The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study Results: Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels Conclusions: Bariatric surgery results in a sustained reduction in transaminase levels and a long-term
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| 10. |
- Burza, Maria Antonella, 1980, et al.
(author)
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PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
- 2012
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In: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 44:12, s. 1037-1041
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Journal article (peer-reviewed)abstract
- Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047). Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity. Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group. Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
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| 11. |
- Carlsson, Lena M S, 1957, et al.
(author)
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ALK7 expression is specific for adipose tissue, reduced in obesity and correlates to factors implicated in metabolic disease.
- 2009
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In: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 382:2, s. 309-14
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Journal article (peer-reviewed)abstract
- Human adipose tissue is a major site of expression of inhibin beta B (INHBB) which homodimerizes to form the novel adipokine activin B. Our aim was to determine if molecules needed for a local action of activin B are expressed in adipose tissue. Microarray analysis showed that adipose tissue expressed activin type I and II receptors and that the expression of activin receptor-like kinase 7 (ALK7) was adipose tissue specific. In obesity discordant siblings from the SOS Sib Pair study, adipose tissue ALK7 expression was higher in lean (n=90) compared to obese (n=90) subjects (p=4 x 10(-31)). Adipose tissue ALK7 expression correlated with several measures of body fat, carbohydrate metabolism and lipids. In addition, ALK7 and INHBB expression correlated but only in lean subjects and in subjects with normal glucose tolerance. We conclude that activin B may have local effects in adipose tissue and thereby influence obesity and its comorbidities.
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| 12. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects.
- 2012
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In: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 367:8, s. 695-704
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Journal article (other academic/artistic)abstract
- Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes.
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| 13. |
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| 14. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
- 2023
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In: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Journal article (peer-reviewed)abstract
- To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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| 15. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study.
- 2017
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In: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279
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Journal article (peer-reviewed)abstract
- Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m(2) or greater in men and 38 kg/m(2) or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.
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| 16. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
- 2019
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In: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
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Journal article (peer-reviewed)abstract
- Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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| 17. |
- Carlsson, Lena M S, 1957, et al.
(author)
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The incidence of albuminuria after bariatric surgery and usual care in swedish obese subjects (SOS): a prospective controlled intervention trial.
- 2015
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39:1, s. 169-175
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Journal article (peer-reviewed)abstract
- Background:Obesity is associated with increased risk of chronic kidney disease and albuminuria is a predictor of renal impairment. Bariatric surgery reduces body weight in obese subjects, but it is not known whether surgery can prevent development of albuminuria. This study aims to determine the long-term effect of bariatric surgery on the incidence of albuminuria.Subjects:The Swedish Obese Subjects study is a non-randomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden. Between 1 September 1987 and 31 January 2001, 2010 participants who underwent bariatric surgery and 2037 controls were recruited. Inclusion criteria were age 37-60 years and BMI⩾34 in men and BMI⩾38 in women. In this analysis, we included 1498 patients in the surgery group and 1610 controls without albuminuria at baseline. Patients in the bariatric surgery group underwent banding (18%), vertical banded gastroplasty (69%) or gastric bypass (13%); controls received usual obesity care. Date of analysis was 1 January 2011. Median follow-up was 10 years, and the rates of follow-up were 87%, 74 and 52% at 2, 10 and 15 years, respectively. The main outcome of this report is incidence of albuminuria (defined as urinary albumin excretion >30mg per 24h) over up to 15 years.Results:During the follow-up, albuminuria developed in 246 participants in the control group and in 126 in the bariatric surgery group, corresponding to incidence rates of 20.4 and 9.4 per 1000 person years, respectively (adjusted hazard ratio, 0.37; 95% confidence interval, 0.30-0.47; P<0.001). The expected number of surgeries needed to prevent the development of albuminuria in one patient at 10 years was nine.Conclusions:Bariatric surgery is associated with reduced incidence of albuminuria compared with usual obesity care.International Journal of Obesity advance online publication, 10 June 2014; doi:10.1038/ijo.2014.72.
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| 18. |
- Christenson, Karin, et al.
(author)
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Endogenous Acute Phase Serum Amyloid A Lacks Pro-Inflammatory Activity, Contrasting the Two Recombinant Variants That Activate Human Neutrophils through Different Receptors.
- 2013
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 4
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Journal article (peer-reviewed)abstract
- Most notable among the acute phase proteins is serum amyloid A (SAA), levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2) that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1) both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2). We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.
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| 19. |
- Gummesson, Anders, 1973, et al.
(author)
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Relations of Adipose Tissue Cell Death-Inducing DFFA-like Effector A Gene Expression to Basal Metabolic Rate, Energy Restriction and Obesity: Population-based and Dietary Intervention Studies.
- 2007
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4759-65
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Journal article (peer-reviewed)abstract
- Context: Cell death-inducing DFFA-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. Objective: To investigate the putative link between CIDEA and basal metabolic rate in humans, and to further elucidate the role of CIDEA in human obesity. Design: We have explored CIDEA gene expression in adipose tissue in two different human studies: A cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n=92), and a longitudinal intervention-study of obese subjects treated with a very low calorie diet (VLCD study, n=24). Results: The CIDEA gene was predominantly expressed in adipocytes as compared to other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age and gender (p=0.014). VLCD induced an increase in adipose tissue CIDEA expression (p<0.0001) with a subsequent decrease in response to refeeding (p<0.0001). Reduced CIDEA gene expression was associated with a high body fat content (p<0.0001) and with high insulin levels (p<0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with BMI-matched controls. In a separate sample of VLCD-treated subjects (n=10), uncoupling protein 1 expression was reduced during diet (p=0.0026) and inversely associated with CIDEA expression (p=0.0014). Conclusion: The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
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| 20. |
- Jacobson, Peter, 1962, et al.
(author)
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9p21.3 Coronary Artery Disease Locus Identifies Patients With Treatment Benefit From Bariatric Surgery in the Nonrandomized Prospective Controlled Swedish Obese Subjects Study.
- 2020
-
In: Circulation. Genomic and precision medicine. - 2574-8300. ; 13:5, s. 460-465
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Journal article (peer-reviewed)abstract
- Sequence variation at chromosome 9p21.3 accounts for 20% of myocardial infarctions (MIs) in several populations. Whereas the risk conferred by the 9p21.3 locus appears to act independently of traditional risk factors, studies suggest that the association between 9p21.3 and MI is modified by glucose homeostasis and lifestyle. We examined if the 9p21.3 variant rs1333049, along with the previously identified predictor fasting insulin, modifies the preventive effect of bariatric surgery on MI incidence.rs1333049 was genotyped in 1852 patients treated by bariatric surgery and 1803 controls given usual care in the SOS study (Swedish Obese Subjects). MI incidence was determined using national registers. Median follow-up was 21 years (interquartile range 18-24 years).Overall, 366 MIs occurred during follow-up. Among rs1333049 risk-allele carriers (CC+GC), the incidence of MI was reduced in the surgery group compared with the control group (hazard ratio=0.72 [95% CI, 0.57-0.92], P=0.008). By contrast, noncarriers (GG) showed no significant differences in MI incidence between the treatment groups (hazard ratio=1.28 [0.86-1.90], P=0.227; interaction between treatment and the risk-allele P=0.016). In addition, carriers with higher fasting insulin (above the median [17 mmol/L]) experienced significantly higher MI incidence than carriers with lower fasting insulin (hazard ratio=0.58 [0.42-0.78], P<0.001, interaction P=0.031).In the SOS cohort, patients with the chromosome 9p21.3 rs1333049 risk allele together with high fasting insulin levels benefitted from bariatric surgery in terms of reduced incidence of MI. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01479452.
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| 21. |
- Jernås, Margareta, 1961, et al.
(author)
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Changes in adipose tissue gene expression and plasma levels of adipokines and acute-phase proteins in patients with critical illness.
- 2009
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In: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 58:1, s. 102-8
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Journal article (peer-reviewed)abstract
- Insulin resistance develops rapidly during critical illness. The release of adipokines from adipose tissue is thought to play a key role in the development of insulin resistance, as are elevated levels of acute-phase proteins. The aim of this study was to identify changes in adipose tissue gene expression and plasma levels of adipokines and acute-phase proteins during critical illness. From 8 patients with subarachnoidal hemorrhage, consecutive blood samples and adipose tissue biopsies were obtained at 3 time points, twice during intensive care (1-2 days [IC1] and 7-9 days after subarachnoidal hemorrhage) and once after 8 months (recovery). The patients received a continuous insulin infusion to maintain normal glucose levels reflecting insulin resistance. The DNA microarray analysis showed increased zink-alpha2 glycoprotein (ZAG) and phospholipase A2, group IIA messenger RNA levels during intensive care compared with recovery (P < .05). Real-time polymerase chain reaction confirmed the increased expression of ZAG and phospholipase A2, group IIA. Plasma levels of ZAG, serum amyloid A, and C-reactive protein were higher at 7 to 9 days after subarachnoidal hemorrhage compared with either IC1 or recovery (P = .0001); and plasma levels of retinol-binding protein 4 and adiponectin were lower at IC1 compared with recovery (P = .05). The described changes in adipose tissue gene expression and plasma levels of adipokines and acute-phase proteins may influence the development of insulin resistance during critical illness.
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| 22. |
- Jernås, Margareta, 1961, et al.
(author)
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Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression
- 2006
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In: The FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 20
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Journal article (peer-reviewed)abstract
- Enlarged adipocytes are associated with insulin resistance and are an independent predictor of type 2 diabetes. To understand the molecular link between these diseases and adipocyte hypertrophy, we developed a technique to separate human adipocytes from an adipose tissue sample into populations of small cells (mean 57.6+-3.54 um) and large cells (mean 100.1+-3.94 um). Microarray analysis of the cell populations separated from adipose tissue from three subjects identified 14 genes, of which five immune-related, with more than fourfold higher expression in large cells than small cells. Two of these genes were serum amyloid A (SAA) and transmembrane 4 L six family member 1 (TM4SF1). Real-time RT-PCR analysis of SAA and TM4SF1 expression in adipocytes from seven subjects revealed 19-fold and 22-fold higher expression in the large cells, respectively, and a correlation between adipocyte size and both SAA and TM4SF1 expression. The results were verified using immunohistochemistry. In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression. Thus, we have identified genes with markedly higher expression in large, compared with small, human adipocytes. These genes may link hypertrophic obesity to insulin resistance/type 2 diabetes.
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| 23. |
- Johansson, K., et al.
(author)
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Long-term risk of anaemia after bariatric surgery: results from the Swedish Obese Subjects study
- 2021
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In: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 9:8, s. 515-524
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Journal article (peer-reviewed)abstract
- Background Nutritional deficiencies, such as iron and vitamin B12 deficiencies, are potential adverse consequences of bariatric surgery. Long-term data on anaemia after bariatric surgery are largely lacking. We aimed to investigate the risk of anaemia, iron and vitamin B12 deficiency anaemia, and vitamin B12 deficiency over 20 years in individuals who had bariatric surgery or received usual obesity care. Methods The prospective, controlled Swedish Obese Subjects study recruited people with obesity via recruitment campaigns in the mass media and at primary health-care centres, and was done at 480 primary health-care centres and in 25 surgical departments in Sweden. Eligible participants were aged 37-60 years and had a BMI of either 34 kg/m(2) or more (for men) or 38 kg/m(2) or more (for women). Participants were excluded if they had undergone previous bariatric surgery or had contraindicating conditions. Two main groups were formed: those who chose bariatric surgery, the type of which was determined by the operating surgeon, and a contemporaneously matched control group, created by use of 18 matching variables, who received usual non-surgical obesity care that ranged from lifestyle advice to no treatment. Haemoglobin concentration was measured during examination visits at baseline and at 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years of follow-up. Anaemia was defined as a haemoglobin concentration of less than 120 g/L for women and 130 g/L for men. The primary, non-specified outcome was the incidence of anaemia, and was assessed in the as-treated population, which comprised only patients who received the actual treatment. The associations between treatment type and anaemia are expressed as unadjusted hazard ratios (HRs) and HRs adjusted for age, sex, BMI, menopausal status, education, diabetes, and hypertension, with 95% CIs. This study is registered in ClinicalTrials.gov, NCT01479452, and is closed to new participants, with follow-up ongoing. Findings Between Sept 1, 1987, and Jan 31, 2001, 6905 individuals were assessed for eligibility, of whom 5335 were eligible. Of these, we included 2007 patients who chose bariatric surgery (266 in the gastric bypass group, 1365 in the vertical-banded gastroplasty group, and 376 in the gastric banding group) and 2040 matched controls who received usual obesity care. During a maximum of 20 years and a median of 10 years (IQR 3-20) of follow-up, there were 133 anaemia events in the gastric bypass group, 359 in the vertical-banded gastroplasty group, 101 in the gastric banding group, and 261 in the control group. Compared with the control group (13 cases per 1000 person-years, 95% CI 11-14), the incidence of anaemia was higher in the gastric bypass group (64 cases per 1000 person-years, 53-74; HR 5.05, 95% CI 3.94-6.48; p<0.0001), the vertical-banded gastroplasty group (23 cases per 1000 personyears, 21-26; 2.67, 2.25-3.18; p<0.0001), and the gastric banding group (26 per 1000 person-years, 21-31; 2.76, 2.15-3.52; p<0.0001). These associations remained after adjustment. Interpretation Our findings highlight the increased risk of anaemia after bariatric surgery and the importance of longterm compliance to nutritional supplementation and monitoring to enable prevention and early detection of serious nutritional deficiencies after bariatric surgery. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
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| 24. |
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| 25. |
- Konttinen, Hanna, et al.
(author)
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Prediction of Suicide and Nonfatal Self-harm After Bariatric Surgery: A Risk Score Based on Sociodemographic Factors, Lifestyle Behavior, and Mental Health: A Nonrandomized Controlled Trial
- 2021
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In: Annals of surgery. - 1528-1140. ; 274:2, s. 339-345
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Journal article (peer-reviewed)abstract
- To identify preoperative sociodemographic and health-related factors that predict higher risk of nonfatal self-harm and suicide after bariatric surgery.Evidence is emerging that bariatric surgery is related to an increased risk of suicide and self-harm, but knowledge on whether certain preoperative characteristics further enhance the excess risk is scarce.The nonrandomized, prospective, controlled Swedish Obese Subjects study was linked to 2 Nationwide Swedish registers. The bariatric surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual care. Participants were recruited from 1987 to 2001, and information on the outcome (a death by suicide or nonfatal self-harm event) was retrieved until the end of 2016. Subhazard ratios (sub-HR) were calculated using competing risk regression analysis.The risk for self-harm/suicide was almost twice as high in surgical patients compared to control patients both before and after adjusting for various baseline factors [adjusted sub-HR = 1.98, 95% confidence interval (CI) = 1.34-2.93]. Male sex, previous healthcare visits for self-harm or mental disorders, psychiatric drug use, and sleep difficulties predicted higher risk of self-harm/suicide in the multivariate models conducted in the surgery group. Interaction tests further indicated that the excess risk for self-harm/suicide related to bariatric surgery was stronger in men (sub-HR = 3.31, 95% CI = 1.73-6.31) than in women (sub-HR = 1.54, 95% CI = 1.02-2.32) (P = 0.007 for adjusted interaction). A simple-to-use score was developed to identify those at highest risk of these events in the surgery group.Our findings suggest that male sex, psychiatric disorder history, and sleep difficulties are important predictors for nonfatal self-harm and suicide in postbariatric patients. High-risk patients who undergo surgery might require regular postoperative psychosocial monitoring to reduce the risk for future self-harm behaviors.
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| 26. |
- Kristensson, Felipe M., et al.
(author)
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Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial
- 2024
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In: JAMA Surgery. - 2168-6254 .- 2168-6262.
-
Journal article (peer-reviewed)abstract
- Importance: Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. Objective: To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. Design, Setting, and Participants: The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). Intervention: In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Main Outcome and Measures: Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. Results: The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P =.019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P =.06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 μIU/L (HR, 0.48; 95% CI, 0.31-0.74; P =.001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P =.008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P =.84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P =.97; interaction P =.02). Conclusions and Relevance: This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia.
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| 27. |
- Lena, Carlsson, et al.
(author)
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Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study.
- 2020
-
In: The New England journal of medicine. - 1533-4406. ; 383:16, s. 1535-1543
-
Journal article (peer-reviewed)abstract
- Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. (Funded by the Swedish Research Council and others; SOS ClinicalTrials.gov number, NCT01479452.).
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| 28. |
- Lohmander, L. S., et al.
(author)
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Bariatric surgery, osteoarthritis and arthroplasty of the hip and knee in Swedish Obese Subjects - up to 31 years follow-up of a controlled intervention study.
- 2023
-
In: Osteoarthritis and cartilage. - : Elsevier BV. - 1522-9653 .- 1063-4584. ; 31:5, s. 636-646
-
Journal article (peer-reviewed)abstract
- To study the long-term effect of obesity and bariatric surgery on incidences of osteoarthritis and arthroplasty of hip and knee.Hazard ratios (HR) and incidence rates (IR) of osteoarthritis and arthroplasty of hip and knee were studied in the prospective, controlled, non-randomized Swedish Obese Subjects (SOS) study (bariatric surgery group, n=2007; matched controls given usual obesity care, n=2040) and the SOS reference cohort (n=1135, general population). Osteoarthritis diagnosis and arthroplasty for osteoarthritis were captured from the National Swedish Patient Register. Median follow-up time was 21.2 (IQR 16.4-24.8), 22.9 (IQR 19.1-25.7), and 20.1 years (IQR 18.7-20.9) for the control group, surgery group and reference cohort, respectively.The surgery group displayed lower incidence of hip osteoarthritis (IR 5.3, 95% CI 4.7-6.1) compared to controls (IR 6.6, 95% CI 5.9-7.5, adjHR 0.83, 95% CI 0.69-1.00) but similar incidence of hip arthroplasty. Similar incidence of knee osteoarthritis was observed in the surgery group and controls, but knee arthroplasty was more common in the surgery group (IR 7.4, 95% CI 6.6-8.2 and 5.6, 95% CI 4.9-6.4, adjHR 1.45, 95% CI 1.22-1.74). The reference cohort displayed lower incidences of osteoarthritis and arthroplasty of hip and knee compared with the surgery group and controls.Bariatric surgery did not normalize the increased risk of knee and hip osteoarthritis in patients with obesity but was associated with an increased incidence of knee arthroplasty compared to the control group. With the limitations inherent to the present data, additional studies are needed to confirm these results.clinicaltrials.gov Identifier: NCT01479452.
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| 29. |
- Maglio, Cristina, 1983, et al.
(author)
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The IRS1 rs2943641 Variant and Risk of Future Cancer Among Morbidly Obese Individuals.
- 2013
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:4
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Journal article (peer-reviewed)abstract
- Context:Obesity and insulin resistance are risk factors for cancer development. The IRS1 rs2943641 genetic variant has been widely associated with insulin resistance.Objective:The aim of the study was to examine whether the IRS1 rs2943641 associates with cancer incidence in obese individuals.Design, Setting and Patients:The IRS1 rs2943641 was genotyped in participants from the Swedish Obese Subjects (SOS) study, an intervention trial on the effect of bariatric surgery on mortality and morbidity compared with usual care and in the population-based Malmö Diet and Cancer (MDC) cohort. In both studies, the median follow-up for cancer incidence was about 15 years.Intervention and Main Outcome Measure:Cancer incidence was assessed in both the SOS and the MDC cohorts through national and local registers.Results:The IRS1 T allele was associated with lower insulin resistance in both the SOS and the MDC studies. A lower cancer incidence was found in T allele carriers from the SOS control group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62-0.96; P = .021) and was restricted to morbidly obese individuals (HR 0.67, 95% CI 0.50-0.91; P = .011). No evidence of such association was detected in the surgery group (interaction P = .005). In the MDC cohort, a nonsignificant tendency for lower cancer incidence in T allele carriers was observed only in morbidly obese individuals. A meta-analysis of morbidly obese individuals (body mass index > 40 kg/m(2)) from the two cohorts strengthened the evidence for the association (HR 0.66, 95% CI 0.50-0.87; P = .004).Conclusions:Our results suggest that the T allele of rs2943641 near IRS1 may associate with lower cancer incidence in morbidly obese individuals.
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| 30. |
- Magnusson, Björn, 1976, et al.
(author)
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Activin B inhibits lipolysis in 3T3-L1 adipocytes
- 2010
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In: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 395:3, s. 373-376
-
Journal article (peer-reviewed)abstract
- Activin B, consisting of two inhibin betaB (INHBB) subunits, is a hormone known to affect gonadal function, reproduction and fetal development. We have reported that INHBB and activin B receptors are highly expressed in adipocytes suggesting that activin B may have local effects in adipose tissue. In this study, we investigate the effect of activin B on lipolysis, measured as release of non-esterified fatty acids and free glycerol. Recombinant activin B decreased lipolysis in a concentration-dependent manner and increased intracellular triglyceride content in 3T3-L1 adipocytes. siRNA-mediated knock down of INHBB expression increased lipolysis, and this effect was abolished by addition of recombinant activin B. In line with its inhibitory effect on lipolysis, activin B caused a down regulation of the expression of adipose triglyceride lipase and hormone sensitive lipase, key genes involved in lipolysis. In summary, we suggest that activin B is a novel adipokine that inhibits lipolysis in a paracrine or autocrine manner.
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| 31. |
- McCulloch, Laura J, et al.
(author)
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COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity.
- 2015
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In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:1, s. 134-46
-
Journal article (peer-reviewed)abstract
- Fibrosis of adipose tissue (AT) increases AT rigidity, reduces its expandability and contributes to metabolic dysfunction. Collagen type VI, alpha3 (COL6A3) encodes one subunit of a fibrotic extracellular matrix (ECM) protein highly expressed in rodent AT. Knock-out of collagen VI in rodent AT led to a significant improvement in metabolic health in obese, diabetic (ob/ob) mice however, it is unknown whether this collagen has the same metabolic significance in human AT. We therefore aimed to undertake a comprehensive assessment of COL6A3 in relation to human AT and obesity. Characterisation of COL6A3 in human AT showed 5 fold higher expression in the stromalvascular fraction compared with adipocyte expression and significantly higher expression in subcutaneous than omental AT. In both depots COL6A3 expression appeared to be lowered in obesity, whilst diet and surgery-induced weight loss increased COL6A3 expression in subcutaneous AT. Leptin treatment caused a dose dependent decrease in COL6A3 expression although no effect was seen with insulin or glucose treatment and no difference observed in subjects with diabetes. In addition, we found that the collagen expression profile in humans differs significantly from rodents as COL6A3 does not appear to be the predominant collagen in adipose, muscle or liver. Our findings oppose those initially seen in rodent studies and most importantly, demonstrate a direct regulation of COL6A3 by leptin. This highlights the importance of a paracrine leptin signalling pathway in human AT and suggests an additional mechanism by which leptin can regulate ECM composition and with it AT expandability.
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| 32. |
- Neovius, Martin, et al.
(author)
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Health Care Use During 20 Years Following Bariatric Surgery
- 2012
-
In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 308:11, s. 1132-1141
-
Journal article (peer-reviewed)abstract
- Context Bariatric surgery results in sustained weight loss; reduced incidence of diabetes, cardiovascular events, and cancer; and improved survival. The long-term effect on health care use is unknown. Objective To assess health care use over 20 years by obese patients treated conventionally or with bariatric surgery. Design, Setting, and Participants The Swedish Obese Subjects study is an ongoing, prospective, nonrandomized, controlled intervention study conducted in the Swedish health care system that included 2010 adults who underwent bariatric surgery and 2037 contemporaneously matched controls recruited between 1987 and 2001. Inclusion criteria were age 37 years to 60 years and body mass index of 34 or higher in men and 38 or higher in women. Exclusion criteria were identical in both groups. Interventions Of the surgery patients, 13% underwent gastric bypass, 19% gastric banding, and 68% vertical-banded gastroplasty. Controls received conventional obesity treatment. Main Outcome Measures Annual hospital days (follow-up years 1 to 20; data capture 1987-2009; median follow-up 15 years) and nonprimary care outpatient visits (years 2-20; data capture 2001-2009; median follow-up 9 years) were retrieved from the National Patient Register, and drug costs from the Prescribed Drug Register (years 7-20; data capture 2005-2011; median follow-up 6 years). Registry linkage was complete for more than 99% of patients (4044 of 4047). Mean differences were adjusted for baseline age, sex, smoking, diabetes status, body mass index, inclusion period, and (for the inpatient care analysis) hospital days the year before the index date. Results In the 20 years following their bariatric procedure, surgery patients used a total of 54 mean cumulative hospital days compared with 40 used by those in the control group (adjusted difference, 15; 95% CI, 2-27; P = .03). During the years 2 through 6, surgery patients had an accumulated annual mean of 1.7 hospital days vs 1.2 days among control patients (adjusted difference, 0.5; 95% CI, 0.2 to 0.7; P < .001). From year 7 to 20, both groups had a mean annual 1.8 hospital days (adjusted difference, 0.0; 95% CI, −0.3 to 0.3; P = .95). Surgery patients had a mean annual 1.3 nonprimary care outpatient visits during the years 2 through 6 vs 1.1 among the controls (adjusted difference, 0.3; 95% CI, 0.1 to 0.4; P = .003), but from year 7, the 2 groups did not differ (1.8 vs 1.9 mean annual visits; adjusted difference, −0.2; 95% CI, −0.4 to 0.1; P = .12). From year 7 to 20, the surgery group incurred a mean annual drug cost of US $930; the control patients, $1123 (adjusted difference, −$228; 95% CI, −$335 to −$121; P < .001). Conclusions Compared with controls, surgically treated patients used more inpatient and nonprimary outpatient care during the first 6-year period after undergoing bariatric surgery but not thereafter. Drug costs from years 7 through 20 were lower for surgery patients than for control patients.
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| 33. |
- Neovius, Martin, et al.
(author)
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Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies.
- 2018
-
In: The lancet. Diabetes & endocrinology. - : Elsevier. - 2213-8595 .- 2213-8587. ; 6:3, s. 197-207
-
Journal article (peer-reviewed)abstract
- Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment.Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts.During 68528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1·78, 95% CI 1·23-2·57; p=0·0021); of these events, nine and three were suicides, respectively (3·06, 0·79-11·88; p=0·11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3·48, 1·65-7·31; p=0·0010), gastric banding (2·43, 1·23-4·82; p=0·011), and vertical-banded gastroplasty (2·25, 1·37-3·71; p=0·0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149582 person-years (median 3·9; IQR 2·8-5·2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3·16, 2·46-4·06; p<0·0001); of these events, 33 and five were suicides, respectively (5·17, 1·86-14·37; p=0·0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0·023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0·0003). The risk of suicide and self-harm was not associated with poor weight loss outcome.Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health.US National Institutes of Health and Swedish Research Council.
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| 34. |
- Olofsson, Louise, 1977, et al.
(author)
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CCAAT/enhancer binding protein alpha (C/EBPalpha) in adipose tissue regulates genes in lipid and glucose metabolism and a genetic variation in C/EBPalpha is associated with serum levels of triglycerides.
- 2008
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:12, s. 4880-6
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Journal article (peer-reviewed)abstract
- CONTEXT: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. OBJECTIVE: The aim of the study was to test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for an association between a polymorphism in C/EBPalpha and metabolic parameters. DESIGN AND METHODS: Adipose tissue C/EBPalpha mRNA expression was analyzed at four time points in obese subjects with (n = 12) and without (n = 12) the metabolic syndrome during caloric restriction (450 kcal/d for 16 wk) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a genetic variation in C/EBPalpha (rs12691) and metabolic parameters was tested in the Swedish Obese Subjects (SOS) study (n = 528) and replicated in Finnish individuals from the Botnia type 2 diabetes study (n = 4,866). RESULTS: During caloric restriction, adipose tissue C/EBPalpha mRNA levels were reduced in subjects with the metabolic syndrome (P = 0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBPalpha regulated the expression of adiponectin; hexokinase 2; lipoprotein lipase; diacylglycerol O-acyltransferase 1 and 2; ATP-binding cassette, sub-family D, member 2; acyl-coenzyme A synthetase long-chain family member 1; CD36; and hydroxysteroid 11-beta dehydrogenase 1. Furthermore, the expression of the human homologs, except adiponectin, correlated to C/EBPalpha mRNA levels in human adipose tissue. The AA genotype of rs12691 was associated with higher serum triglyceride levels in the SOS study (P = 0.022), and this association was replicated in the Botnia study (P = 0.041). CONCLUSIONS: Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.
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| 35. |
- Olofsson, Louise, 1977, et al.
(author)
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Preliminary report: Zn-alpha2-glycoprotein genotype and serum levels are associated with serum lipids.
- 2010
-
In: Metabolism. - : Elsevier BV. - 1532-8600 .- 0026-0495. ; 59:9, s. 1316-1318
-
Journal article (peer-reviewed)abstract
- Zn-alpha2-glycoprotein (ZAG) is a serum protein implicated in cancer cachexia and lipolysis. Our aim was to investigate serum levels of ZAG and polymorphisms in the ZAG gene in relation to serum lipids in man. Serum levels of ZAG correlated with serum levels of cholesterol (P = .00088) in healthy subjects and during weight loss (P = .059). The ZAG genotype was associated with total cholesterol (P = .014) and low-density lipoprotein cholesterol (P = .026) in healthy subjects, and the associations were replicated in an additional cohort (P = .0017 and P = .060, respectively). Our data indicate that ZAG plays a role in lipid metabolism.
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| 36. |
- Olsson, Maja, 1975, et al.
(author)
-
Establishment of a transgenic mouse model specifically expressing human serum amyloid a in adipose tissue.
- 2011
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5
-
Journal article (peer-reviewed)abstract
- Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n=7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n=10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA.
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| 37. |
- Olsson, Maja, 1975, et al.
(author)
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Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors.
- 2011
-
In: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 60:1, s. 114-20
-
Journal article (peer-reviewed)abstract
- The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular disease. In this study, we analyzed SELS expression in subcutaneous adipose tissue and SELS genotype in relation to metabolic risk factors. DNA microarray expression analysis was used to study the expression of SELS in lean and obese siblings from the Swedish Obese Subjects Sib Pair Study. TaqMan genotyping was used to analyze 3 polymorphisms, previously found to be associated with circulating levels of inflammatory markers, in the INTERGENE case-control study of myocardial infarction and unstable angina pectoris. Possible associations between SELS genotype and/or expression with anthropometry and measures of metabolic status were investigated. Real-time polymerase chain reaction was used to analyze the SELS expression in isolated human adipocytes incubated with insulin. In lean subjects, we found correlations between SELS gene expression in subcutaneous adipose tissue and measures of obesity (waist, P = .045; sagittal diameter, P = .031) and blood pressure (diastolic, P = .016; systolic P = .015); and in obese subjects, we found correlations with measures of obesity (body mass index, P = .03; sagittal diameter, P = .008) and glycemic control (homeostasis model assessment of insulin resistance, P = .011; insulin, P = .009) after adjusting for age and sex. The 5227GG genotype was associated with serum levels of insulin (P = .006) and homeostasis model assessment of insulin resistance (P = .007). The expression of SELS increased after insulin stimulation in isolated human adipocytes (P = .008). In this study, we found an association between both SELS gene expression in adipose tissue and SELS genotype with measures of glycemic control. In vitro studies demonstrated that the SELS gene is regulated by insulin in human subcutaneous adipocytes. This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance.
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| 38. |
- Palming, Jenny, 1975, et al.
(author)
-
The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction.
- 2007
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2346-52
-
Journal article (peer-reviewed)abstract
- CONTEXT: We have previously identified nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1), an enzyme involved in the protection against oxidative stress, as a gene predominantly expressed in human adipocytes. Studies in mice deficient in NQO1 activity suggest that NQO1 may also play an important role in metabolism. OBJECTIVE: The aim of this study was to explore the expression and regulation of NQO1 in human adipose tissue (AT) and isolated adipocytes. PATIENTS AND RESULTS: The high expression of NQO1 in adipocytes was verified in human adipocytes and AT by real-time PCR. DNA microarray analysis showed that NQO1 was expressed at higher levels in large compared with small adipocytes, isolated from the same fat biopsy. Furthermore, NQO1 mRNA levels were positively correlated with adipocyte size (n = 7; P < 0.002). During an 18-wk diet regime (n = 24; mean weight loss 27 kg), the NQO1 expression in human sc AT was down-regulated (P < 0.0001), and mRNA levels correlated with body mass index (P = 0.0005), sc, and total abdominal AT areas, as determined by computerized tomography (P < 0.0001, both) and metabolic parameters. NQO1 mRNA levels were also positively correlated with aspartate aminotransferase (P = 0.0028) and alanine aminotransferase (P = 0.0219), markers known to be associated with severity of hepatic steatosis. CONCLUSIONS: NQO1 is highly expressed in human AT, particularly in large adipocytes. AT NQO1 expression is reduced during diet-induced weight loss, and the expression levels positively correlate with adiposity, glucose tolerance, and markers of liver dysfunction. Together, these findings indicate a role for NQO1 in the metabolic complications of human obesity.
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| 39. |
- Parzer, Verena, et al.
(author)
-
Development of a BMI-Assigned Stunkard Scale for the Evaluation of Body Image Perception Based on Data of the SOS Reference Study.
- 2021
-
In: Obesity facts. - : S. Karger AG. - 1662-4033 .- 1662-4025. ; 14:4, s. 397-404
-
Journal article (peer-reviewed)abstract
- Stunkard's figure rating scale is a widely used tool to assess weight status and, more recently, body image perception in people with obesity. However, large population-based studies on Europeans linking this scale's silhouettes with measured BMI values are lacking. Therefore, we used measured weight and height data from the Swedish Obese Subjects (SOS) reference cohort to assign a mean BMI to each of the 9 Stunkard Scale silhouettes and to define silhouette cutoff values for categorizing people with obesity and overweight.A total of 1,128 participants from the SOS reference cohort were included (54% females, BMI = 25.2 [ranging from 17.6 to 45.4] ±3.8 kg/m2, and age = 50 [ranging from 36 to 62] ±7 years [means ± standard deviation]). Patients estimated their own body size by choosing a silhouette of the Stunkard Scale. A mean BMI, based on measured weight and height, was assigned to each male and female silhouette of the Stunkard Scale. Measured BMI values were compared with BMI values calculated by simple linear regression analysis. ROC analysis was used to test accuracy of discrimination and the Youden index to assess optimal cutoff.Figure ratings and BMI were strongly correlated in men, r (518) = 0.76, p < 0.001 and women, r (606) = 0.80, p < 0.001. Silhouette selection significantly predicted BMI values in men, β = 16.03, t (518) = 25.30, p < 0.001, and women, β = 12.06, t (606) = 32.98, p < 0.001, and explained a significant proportion of variance in BMI values in men, R2 = 0.55, F (1, 518) = 639.98, p < 0.001, and women, R2 = 0.64, F (1, 606) = 1,087.88, p < 0.001. ROC curve analyses resulted in an optimal cutoff value of 6 for identifying people with obesity and 5 for overweight.Stunkard's figure rating scale can be used with confidence to assess weight status. Silhouette selection accurately classifies subjects as overweight or obese.
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| 40. |
- Parzer, Verena, et al.
(author)
-
Perceived Body Size in Relation to 10-Year Weight Change in the Swedish Obese Subjects Intervention Study
- 2024
-
In: OBESITY FACTS. - 1662-4025 .- 1662-4033. ; 17:1, s. 81-89
-
Journal article (peer-reviewed)abstract
- Introduction: Body size underestimation in patients with obesity may be associated with long-term weight increase. In the current report, we analyse changes in body size perception in patients with obesity undergoing either bariatric surgery or usual obesity care, and in subgroups of patients who gain weight or maintain their body weight over 10 years. Materials and Methods: A total of 2,504 patients with obesity from the prospective, controlled Swedish Obese Subjects (SOS) intervention study were included in this report, 1,370 patients underwent bariatric surgery and 1,134 patients were usual care controls. Weight was measured and body size was self-estimated using the Stunkard's figure rating scale at baseline and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years of follow-up. A body perception index (BPI) was calculated as estimated/measured BMI. Weight (re)gain was defined as >= 10% increase between 1 and 10 years of follow-up. Results: Body size was underestimated by 12% in the surgery and 14% in the control group (i.e., >5 BMI units) at baseline and underestimation largely persisted over 10 years in both intervention groups. When stratified by long-term weight development, weight regainers from the surgery group underestimated their body size to a larger degree compared to weight maintainers (12 vs. 9%, p < 0.001) after 10 years. Likewise weight gainers in the control group also underestimated their body size to a larger degree (17% vs. 13%, p < 0.001). In both groups, the change in BPI was significantly different between weight regainers and maintainers during follow-up (time-BPI interactions both p < 0.001). Conclusion: Patients with obesity underestimate their body size and this underestimation remains long-term even after major weight loss induced by bariatric surgery. In patients with obesity who maintain their weight, regardless of treatment, underestimation of body size persists but body size perception is slightly more accurate compared to patients who gain or regain weight long-term.
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| 41. |
- Pastel, E., et al.
(author)
-
Lysyl oxidase and adipose tissue dysfunction
- 2018
-
In: Metabolism - Clinical and Experimental. - : Elsevier BV. - 0026-0495. ; 78, s. 118-127
-
Journal article (peer-reviewed)abstract
- Background/objectives. Lysyl oxidase (LOX) is an enzyme crucial for collagen fibre crosslinking and thus for fibrosis development. Fibrosis is characterised by a surplus of collagen fibre accumulation and is amongst others also a feature of obesity-associated dysfunctional adipose tissue (AT) which has been linked with type 2 diabetes. We hypothesised that in type 2 diabetes and obesity LOX expression and activity will be increased as a consequence of worsening AT dysfunction. This study aimed to provide a comprehensive characterisation of LOX in human AT. Methods. LOX mRNA expression was analysed in omental and abdominal subcutaneous AT obtained during elective surgery from subjects with a wide range of BMI, with and without diabetes. In addition, LOX expression was studied in subcutaneous AT before and 9.5 months after bariatric surgery. To study the mechanism of LOX changes, its expression and activity were assessed after either hypoxia, recombinant human leptin or glucose treatment of AT explants. In addition, LOX response to acute inflammation was tested after stimulation by a single injection of lipopolysaccharide versus saline solution (control) in healthy men, in vivo. Quantity of mRNA was measured by RT-qPCR. Results. LOX expression was higher in obesity and correlated with BMI whilst, in vitro, leptin at high concentrations, as a potential feedback mechanism, suppressed its expression. Neither diabetes status, nor hyperglycaemia affected LOX. Hypoxia and lipopolysaccharide-induced acute inflammation increased LOX AT expression, latter was independent of macrophage infiltration. Conclusions. Whilst LOX may not be affected by obesity-associated complications such as diabetes, our results confirm that LOX is increased by hypoxia and inflammation as underlying mechanism for its upregulation in adipose tissue with obesity. (C) 2017 Elsevier Inc. All rights reserved.
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| 42. |
- Pereira, Maria J., 1981-, et al.
(author)
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Human adipose tissue gene expression of solute carrier family 19 member 3 (SLC19A3); relation to obesity and weight-loss
- 2022
-
In: Obesity Science & Practice. - : Wiley. - 2055-2238. ; 8:1, s. 21-31
-
Journal article (peer-reviewed)abstract
- Objective: Adipose tissue is a specialized endocrine organ that is involved in modulating whole-body energy homeostasis and expresses a specific subset of genes, which may play a role in adipose tissue metabolism. The aim of this study was to search for novel adipose tissue-specific genes using a tissue panel of RNAseq expression profiles. Methods: RNAseq expression profiles from 53 human tissues were downloaded from the GTex database. SLC19A3 expression was analyzed by microarray or real-time PCR in two sets of paired subcutaneous and omental adipose tissue samples, in two studies with adipose tissue from persons with high or low body mass index (BMI), in adipose tissue from patients who underwent weight loss with a very-low caloric diet and during preadipocyte-adipocyte differentiation. Results: The RNAseq-based tissue distribution expression screen identified SLC19A3 (encoding the thiamine transporter 2) as adipose tissue-specific. SLC19A3 expression was higher in subcutaneous compared with omental adipose tissue in both sample sets (p = 0.043 and p < 0.001). Preadipocyte differentiation towards adipocytes resulted in increased SLC19A3 gene expression (p = 0.018 or less at all-time points). Subcutaneous adipose tissue expression of SLC19A3 was lower in persons with high BMI in both cohorts (p = 0.008, and p < 0.001) and increased during a weight-loss intervention (p = 0.006). Conclusion: The specific adipose tissue expression pattern of SLC19A3, together with its regulation in obesity and during weight loss, indicate that it plays a key role in adipocyte metabolism.
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| 43. |
- Romeo, Stefano, 1976, et al.
(author)
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Cardiovascular Events After Bariatric Surgery in Obese Subjects With Type 2 Diabetes
- 2012
-
In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:12, s. 2613-2617
-
Journal article (peer-reviewed)abstract
- OBJECTIVE-Obese individuals with type 2 diabetes have an increased risk of cardiovascular disease. The effect of bariatric surgery on cardiovascular events in obese individuals with type 2 diabetes remains to be determined. The Swedish Obese Subjects (SOS) study is a prospective, controlled intervention study that examines the effects of bariatric surgery on hard end points. The aim of the present study was to examine the effect of bariatric surgery on cardiovascular events in the SOS study participants with type 2 diabetes. RESEARCH DESIGN AND METHODS-All SOS study participants with type 2 diabetes at baseline were included in the analyses (n = 345 in the surgery group and n = 262 in the control group). Mean follow-up was 13.3 years (interquartile range 10.2-16.4) for all cardiovascular events. RESULTS-Bariatric surgery was associated with a reduced myocardial infarction incidence (38 events among the 345 subjects in the surgery group vs. 43 events among the 262 subjects in the control group; log-rank P = 0.017; adjusted hazard ratio [HR] 0.56 [95% CI 0.34-0.93]; P = 0.025). No effect of bariatric surgery was observed on stroke incidence (34 events among the 345 subjects in the surgery group vs. 24 events among the 262 subjects in the control group; log-rank P = 0.852; adjusted HR 0.73 [0.41-1.30]; P = 0.29). The effect of surgery in reducing myocardial infarction incidence was stronger in individuals with higher serum total cholesterol and triglycerides at baseline (interaction P value = 0.02 for both traits). BMI (interaction P value = 0.12) was not related to the surgery outcome. CONCLUSIONS-Bariatric surgery reduces the incidence of myocardial infarction in obese individuals with type 2 diabetes. Preoperative BMI should be integrated with metabolic parameters to maximize the benefits of bariatric surgery.
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| 44. |
- Saiki, Atsuhito, et al.
(author)
-
Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss.
- 2009
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:10, s. 3987-94
-
Journal article (peer-reviewed)abstract
- CONTEXT: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in hypovascular connective tissues. Global gene expression scans show that the TNMD gene also is expressed in human adipose tissue and that its expression is regulated in response to weight reduction; however, more detailed information is lacking. OBJECTIVE: The aim of this study was to investigate TNMD tissue distribution and TNMD gene expression in human adipose tissue in relation to obesity and metabolic disease. DESIGN, PATIENTS, AND INTERVENTIONS: TNMD gene expression, tissue distribution, and TNMD gene expression in adipose tissue from different depots, from lean and obese subjects, and during diet-induced weight reduction were analyzed by DNA microarray and real-time PCR. MAIN OUTCOME MEASURE: We primarily measured TNMD gene expression. RESULTS: The TNMD gene was predominantly expressed in sc adipose tissue. TNMD gene expression was higher in sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P = 0.014). In both women and men, TNMD gene expression was significantly higher in the obese subjects compared to the lean subjects (P = 1.1 x 10(-26) and P = 0.010, respectively). In a multiple linear regression analysis, BMI was a significant independent predictor of TNMD gene expression. TNMD gene expression was down-regulated during diet-induced weight loss, with a 65% decrease after 18 wk of diet (P < 0.0001). CONCLUSIONS: We conclude that human adipose tissue TNMD gene expression is highly affected by obesity, adipose tissue location, and weight loss, indicating that TNMD may play a role in adipose tissue function.
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| 45. |
- Shulman, Alexander, 1978, et al.
(author)
-
Incidence of end-stage renal disease following bariatric surgery in the Swedish Obese Subjects Study.
- 2018
-
In: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 42, s. 964-973
-
Journal article (peer-reviewed)abstract
- Obesity is a major public health problem leading to co-morbidities such as diabetes, hypertension and kidney failure. Bariatric surgery results in pronounced and maintained weight loss and prevention of obesity-related diseases and their complications. Most studies of bariatric surgery on kidney disease show improvements after surgery. However, long-term studies analyzing hard end-points are lacking. Here we report on the long-term effects of bariatric surgery compared to usual obesity care on incidence of end-stage renal disease (ESRD) alone and in combination with chronic kidney disease stage 4 (CKD4/ESRD).4047 patients were included in the Swedish Obese Subjects (SOS) study. Inclusion criteria were age 37-60 years and BMI≥34 in men and BMI≥38 in women. Patients in the bariatric surgery group (N=2010) underwent banding (18%), vertical banded gastroplasty (69%), or gastric bypass (13%); controls (N=2037) received usual obesity care. In this analysis, patients were followed up for a median time of 18 years. The incidence of ESRD and CKD4 was obtained by crosschecking the SOS database with the Swedish National Patient Register.During follow-up, ESRD occurred in 13 patients in the surgery group and in 26 patients in the control group (adjusted hazard ratio (HR)=0.27; 95% CI 0.12-0.60; p=0.001). The number of CKD4/ESRD events was 23 in the surgery group and 39 in the control group (adjusted HR=0.33; 95% CI 0.18-0.62; p<0.001). In both analyses, bariatric surgery had a more favorable effect in patients with baseline serum insulin levels above median compared to those with lower insulin levels (interaction p=0.010). Treatment benefit of bariatric surgery was also greater in patients with macroalbuminuria at baseline compared to those without macroalbuminuria (interaction p<0.001).Our study showed for the first time that bariatric surgery is associated with a long-term protection against ESRD and CKD4/ESRD.
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| 46. |
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| 47. |
- Sjöholm, Kajsa, 1971, et al.
(author)
-
A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A.
- 2005
-
In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:4, s. 2233-9
-
Journal article (peer-reviewed)abstract
- To identify genes predominantly expressed in omental adipocytes, microarray expression profiles from 33 human tissues or cell types were analyzed, using an algorithm developed for identification of transcripts predominantly expressed in a certain tissue. Both known adipocyte-specific and more unexpected genes were among the 28 genes identified. To validate the approach, adipocyte expression of three of these genes, acute-phase serum amyloid A (A-SAA), aquaporin 7, and transport secretion protein-2.2, was compared with 17 other human tissues by real-time PCR. The unexpectedly high expression of A-SAA in adipocytes was further verified by Northern blot and immunohistochemistry. The liver, reported to be the main production site for A-SAA, displayed the second highest expression using microarray and real-time PCR. In obese subjects, adipose tissue mRNA and serum A-SAA levels were down-regulated during an 18-wk diet regime (P < 0.05 and P < 0.0001, respectively). A-SAA serum levels were highly correlated to adipose tissue mRNA levels (P < 0.001) and to the total (P < 0.0001) and sc (P < 0.0001) adipose tissue areas, as analyzed by computed tomography. We show that adipose tissue is a major expression site of A-SAA during the nonacute-phase reaction condition. This provides a direct link between adipose tissue mass and a marker for low-grade inflammation and cardiovascular risk.
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| 48. |
- Sjöholm, Kajsa, 1971, et al.
(author)
-
Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-Term Results From the Swedish Obese Subjects Study.
- 2022
-
In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:2, s. 444-450
-
Journal article (peer-reviewed)abstract
- Obesity and type 2 diabetes are associated with serious adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study.The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of whom underwent bariatric surgery and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years).During follow-up, the incidence rate for first-time cancer was 9.1 per 1,000 person-years (95% CI 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1,000 person-years (95% CI 11.2-17.7) in patients treated with usual obesity care (adjusted hazard ratio 0.63 [95% CI 0.44-0.89], P = 0.008). Moreover, surgery was associated with reduced cancer incidence in women (0.58 [0.38-0.90], P = 0.016), although the sex-treatment interaction was nonsignificant (P = 0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (0.40 [0.22-0.74], P = 0.003).These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk.
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| 49. |
- Sjöholm, Kajsa, 1971, et al.
(author)
-
Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: differences between men and women.
- 2009
-
In: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 48:3, s. 260-6
-
Journal article (peer-reviewed)abstract
- The aim of this study was to characterize the association between adipocyte enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we wanted to search for possible associations with measures of glycemic control and levels of circulating adipokines and/or inflammatory markers in men and women with a large range in body mass index. The study cohort consisted of 167 subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin, interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured. Women had higher serum levels of SAA than men (p=0.044). SAA levels were weakly but positively correlated with BMI (p=0.043) and % body fat (p=0.027) in all subjects as well as subcutaneous adipocyte diameter (p=0.034) in women. Furthermore, in all subjects we found correlations between SAA levels and levels of CRP (p<0.001), interleukin-6 (p<0.001), leptin (p=0.003), insulin (p=0.006), HbA1c (p=0.02) and HOMA-IR (p=0.002). A majority of the correlations were strongest in women. In conclusion, serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control. There seems to be large sex differences in these associations suggesting that sex-specific factors need to be considered when analyzing SAA levels in relation to metabolic disease.
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| 50. |
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