| 1. |
- Benzinou, Michael, et al.
(författare)
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Common nonsynonymous variants in PCSK1 confer risk of obesity.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:8, s. 943-5
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
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| 2. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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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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Ingår i: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Dina, Christian, et al.
(författare)
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Variation in FTO contributes to childhood obesity and severe adult obesity.
- 2007
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:6, s. 724-6
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Tidskriftsartikel (refereegranskat)abstract
- We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.
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| 6. |
- Jamaly, Shabbar, 1965, et al.
(författare)
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Bariatric Surgery and the Risk of New-Onset Atrial Fibrillation in SwedishObese Subjects.
- 2016
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 68:23, s. 2497-2504
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a risk factor for atrial fibrillation, which in turn is associated with stroke, heart failure, and increased all-cause mortality.The authors investigated whether weight loss through bariatric surgery may reduce the risk of new-onset atrial fibrillation.SOS (Swedish Obese Subjects) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary healthcare centers in Sweden. The cohort was recruited between 1987 and 2001. Among 4,021 obeseindividuals with sinus rhythm and no history of atrial fibrillation, 2,000 underwent bariatric surgery (surgery group), and 2,021 matched obese control subjects received usual care (control group). The outcome, first-time atrial fibrillation, was ascertained by crosschecking the SOS database with the Swedish National Patient Register on inpatientand outpatient diagnosis codes.During a median follow-up of 19 years, first time atrial fibrillation occurred in 247 patients (12.4%) in the surgical group, and in 340 (16.8%) control subjects. The risk of developing atrial fibrillation was 29% lower in the surgery group versus the control group (hazard ratio: 0.71; 95% confidence interval: 0.60 to 0.83; p< 0.001). Younger individuals benefited more from surgical intervention than those who were older (p value for interaction 0.001). Also, those with a high diastolic blood pressure benefitted more from surgery than did those with a low diastolic blood pressure (p for interaction= 0.028).Compared with usual care, weight loss through bariatric surgery reduced the risk of atrial fibrillationamong persons being treated for severe obesity. The risk reduction was more apparent in younger people and in thosewith higher blood pressure.
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| 7. |
- Jamaly, Shabbar, 1965, et al.
(författare)
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Surgical obesity treatment and the risk of heart failure.
- 2019
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:26, s. 2131-2138
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with increased risk for heart failure. We analysed data from the Swedish Obese Subjects (SOS) study, a prospective matched cohort study, to investigate whether bariatric surgery reduces this risk.From the total SOS population (n=4047), we identified 4033 obese individuals with no history of heart failure at baseline, of whom 2003 underwent bariatric surgery (surgery group) and 2030 received usual care (control group). First-time principal diagnoses of heart failure were identified by crosschecking the SOS database with the Swedish National Patient Register and the Swedish Cause of Death Register using diagnosis codes. During a median follow-up of 22years, first-time heart failure occurred in 188 of the participants treated with surgery and in 266 of those receiving usual care. The risk of developing heart failure was lower in the surgery group than in the control group [sub-hazard ratio 0.65, 95% confidence interval (CI) 0.54-0.79; P<0.001]. After pooling data from the two study groups, the quartile of subjects with the largest weight loss after 1 year (mean -41kg) displayed the greatest risk reduction (sub-hazard ratio 0.51, 95% CI 0.30-0.70; P<0.001). This association remained statistically significant after adjustment for surgical intervention and potential baseline confounders (sub-hazard ratio 0.60, 95% CI 0.36-0.97; P=0.038).Compared with usual care, bariatric surgery was associated with reduced risk of heart failure among persons being treated for obesity. The risk of heart failure appeared to decline in parallel with a greater degree of weight loss.NCT01479452.
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| 8. |
- Jernås, Margareta, 1961, et al.
(författare)
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Regulation of carboxylesterase 1 (CES1) in human adipose tissue.
- 2009
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 383:1, s. 63-7
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Tidskriftsartikel (refereegranskat)abstract
- Carboxylesterase 1 (CES1) has recently been suggested to play a role in lipolysis. Our aim was to study the regulation of CES1 expression in human adipose tissue. In the SOS Sib Pair Study, CES1 expression was higher in obese compared with lean sisters (n=78 pairs, P=8.7x10(-18)) and brothers (n=12 pairs, P=0.048). CES1 expression was higher in subcutaneous compared with omental adipose tissue in lean (P=0.027) and obese subjects (P=0.00036), and reduced during diet-induced weight loss (n=24, weeks 8, 16, and 18 compared to baseline, P<0.0001 for all time points). CES1 expression was higher in isolated adipocytes compared with intact adipose tissue (P=0.0018) and higher in large compared with small adipocytes (P=4.1x10(-6)). Basal and stimulated lipolysis was not different in individuals with high, intermediate, and low expression of CES1. Thus, CES1 expression was linked to body fat and adipocyte fat content but not to lipolytic activity.
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| 9. |
- Mardinoglu, Adil, 1982, et al.
(författare)
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Integration of clinical data with a genome-scale metabolic model of the human adipocyte
- 2013
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292 .- 1744-4292. ; 9, s. 649-
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the presence/absence of proteins encoded by 14 077 genes in adipocytes obtained from different tissue samples using immunohistochemistry. By combining this with previously published adipocyte-specific proteome data, we identified proteins associated with 7340 genes in human adipocytes. This information was used to reconstruct a comprehensive and functional genome-scale metabolic model of adipocyte metabolism. The resulting metabolic model, iAdipocytes1809, enables mechanistic insights into adipocyte metabolism on a genome-wide level, and can serve as a scaffold for integration of omics data to understand the genotype-phenotype relationship in obese subjects. By integrating human transcriptome and fluxome data, we found an increase in the metabolic activity around androsterone, ganglioside GM2 and degradation products of heparan sulfate and keratan sulfate, and a decrease in mitochondrial metabolic activities in obese subjects compared with lean subjects. Our study hereby shows a path to identify new therapeutic targets for treating obesity through combination of high throughput patient data and metabolic modeling.
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| 10. |
- Nookaew, Intawat, 1977, et al.
(författare)
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Adipose Tissue Resting Energy Expenditure and Expression of Genes Involved in Mitochondrial Function Are Higher in Women than in Men.
- 2013
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:2
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Tidskriftsartikel (refereegranskat)abstract
- Context:Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment.Objective:The objective of the study was a search for sex differences in adipose tissue function.Design and Setting:This was an exploratory study performed at a university hospital.Participants and Main Outcome Measures:Resting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732).Results:The relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 × 10(-7)), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256).Conclusions:The increased expression of the brown adipocyte marker uncoupling protein 1 in women indicates that the higher relative contribution of the fat mass to RMR in women is in part explained by an increased number of brown adipocytes.
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