| 1. |
- Mannerås, Louise, 1980, et al.
(författare)
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A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome.
- 2007
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:8, s. 3781-91
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a "hyperplastic" theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.
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| 2. |
- Alexanderson, Camilla, 1978, et al.
(författare)
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Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats: comparisons with estradiol and dihydrotestosterone.
- 2007
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:11, s. 5369-76
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Tidskriftsartikel (refereegranskat)abstract
- Postnatal events contribute to features of the metabolic syndrome in adulthood. In this study, postnatally administered testosterone reduced insulin sensitivity and increased the mesenteric fat depot, the size of mesenteric adipocytes, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and the atherogenic index in adult female rats. To assess the involvement of estrogen and androgen receptors in these programming effects, we compared testosterone-exposed rats to rats exposed to estradiol or dihydrotestosterone (DHT). Estradiol-treated rats had lower insulin sensitivity than testosterone-treated rats and, like those rats, had enlarged mesenteric adipocytes and increased triglyceride levels. DHT also reduced insulin sensitivity but did not mimic the other metabolic effects of testosterone. All treated rats were probably anovulatory, but only those treated with testosterone had reduced testosterone levels. This study confirms our previous finding that postnatal administration of testosterone reduces insulin sensitivity in adult female rats and shows that this effect is accompanied by unfavorable changes in mesenteric fat tissue and in serum lipid levels. The findings in the estradiol and DHT groups suggest that estrogen receptors exert stronger metabolic programming effects than androgen receptors. Thus, insults such as sex hormone exposure in early life may have long-lasting effects, thereby creating a predisposition to disturbances in insulin sensitivity, adipose tissue, and lipid profile in adulthood.
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| 3. |
- Behre, Carl Johan, 1968, et al.
(författare)
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Dissociation between adipose tissue expression and serum levels of adiponectin during and after diet-induced weight loss in obese subjects with and without the metabolic syndrome
- 2007
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Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 56:8, s. 1022-8
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to examine if dysmetabolic subjects (MetS+) have lower adiponectin gene expression and lower circulating adiponectin levels than non-dysmetabolic obese subjects (MetS-) at baseline, if adiponectin expression and adiponectin concentration rise more in the dysmetabolic group during weight loss, and if v-SNARE Vti1a (vesicle transport soluble NSF attachment protein receptor vps10p tail interacting 1a) expression increases during the weight loss, as a mechanism for increased adiponectin secretion. Twenty-one obese MetS+ and 19 obese MetS- subjects underwent a very low-energy diet for 16 weeks followed by 2 weeks of refeeding. Abdominal subcutaneous adipose tissue biopsies and blood samples were taken before, during, and after dieting for DNA microarray, reverse transcriptase-polymerase chain reaction, and biochemical analyses. Serum adiponectin was also assessed in a sex- and age-matched healthy, nonobese reference group. Weight decreased by 26.3+/-9.8 kg in the MetS+ group and 28.2+/-8.4 kg in the MetS- group with concomitant reductions in insulin, hemoglobin A1c, and triglycerides that were more pronounced in the MetS+ group. Initially, the MetS+ subjects had lower serum adiponectin, but the differences disappeared at week 8, with a continuous increase in serum adiponectin throughout the study in both groups to a level that was higher than in the reference group. The expression of adiponectin and v-SNARE Vti1a did not differ between the groups or over time. In conclusion, obese subjects with the metabolic syndrome had lower circulating adiponectin than subjects without the syndrome. Weight loss increased serum levels of adiponectin without a parallel increase in adiponectin gene expression. The mechanisms involved in the regulation of adiponectin levels merits further investigation.
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| 4. |
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| 5. |
- Berry, Max, 1969, et al.
(författare)
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The use of virtual reality for training in carotid artery stenting: a construct validation study
- 2008
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Ingår i: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 49:7, s. 801-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Given that carotid artery stenosis (CAS) intervention is procedurally difficult, possesses an extensive learning curve, and involves a grave list of potential complications, construct validation of new non-clinical training devices is of increasing importance. Purpose: To evaluate the construct validity of the Procedicus-Virtual Interventional Simulator Trainer (Procedicus-VIST) and its use as a training tool. Material and Methods: Sixteen interventionalists (15 males, one female; mean interventional radiology [IR] experience >11 years) and 16 medical students (15 males, one female; no IR experience) received 1 hour of didactic instruction followed by an hour of familiarization training. Subjects then attempted to complete a carotid artery stenting procedure within 1 hour while their performance metrics were recorded. All participants completed a qualitative exit survey of subjective parameters using a visual analog scale. Results: Procedure and fluoroscopic time was 8.7 and 8.7 min greater in the novice group (P=0.0066 and P=0.0031), respectively. There were no significant differences in performances between the two groups in the remaining metrics of cine loops (number recorded), tool/vessel ratio, coverage percentage, and placement accuracy or residual stenosis. Contrast measurement metrics were found to be too imprecise for statistical analysis. Experienced and novice opinions differed significantly for six of 10 subjective parameters. No statistically significant difference in video-gaming habits was demonstrated. Conclusion: With the exception of the metrics of performance time and fluoroscopic use, construct validity of the Procedicus-VIST carotid metrics were not confirmed. Virtual reality simulation as a training method was valued more by novices than by experienced interventionalists.
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| 6. |
- Carlsson, Björn, 1958, et al.
(författare)
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Differences in associations between HSD11B1 gene expression and metabolic parameters in subjects with and without impaired glucose homeostasis
- 2010
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 88:3, s. 252-258
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Animal studies indicate a role for 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity. The association to glucose homeostasis is less clear. We investigated the relationship between HSD11B1 mRNA levels in adipose tissue and in skeletal muscle and anthropometric and metabolic measurements in humans with and without impaired glucose homeostasis. Methods: Twelve obese subjects with impaired glucose homeostasis (MetS+) and 12 obese controls (MetS-) received a Very Low Calorie Diet for 16 weeks and adipose tissue biopsies, blood samples and measurements were obtained. In a second cohort, skeletal muscle biopsies, blood samples and measurements were obtained from 18 subjects with type 2 diabetes (T2DM) and 17 subjects with normal glucose tolerance (NGT). Gene expression was measured by DNA microarray in both studies. Results: HSD11B1 mRNA levels were reduced during diet, and anthropometric measurements and metabolic parameters were associated with HSD11B1 mRNA levels in the MetS-group. However, in the MetS+ group these associations were lost or in opposite direction. This difference was also observed in skeletal muscle between T2DM and NGT. Conclusions: HSD11B1 mRNA levels are associated with metabolic parameters and anthropometric measurements in subjects with normal glucose homeostasis but not in subjects with impaired glucose homeostasis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 7. |
- Gummesson, Anders, 1973, et al.
(författare)
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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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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4759-65
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Jernås, Margareta, 1961, et al.
(författare)
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Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression
- 2006
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Ingår i: The FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 20
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Tidskriftsartikel (refereegranskat)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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| 9. |
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| 10. |
- Magnusson, Björn, 1976, et al.
(författare)
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Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
- 2008
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Ingår i: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13
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Tidskriftsartikel (refereegranskat)abstract
- Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
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| 11. |
- Olofsson, Louise, 1977, et al.
(författare)
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Preliminary report: Zn-alpha2-glycoprotein genotype and serum levels are associated with serum lipids.
- 2010
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Ingår i: Metabolism. - : Elsevier BV. - 1532-8600 .- 0026-0495. ; 59:9, s. 1316-1318
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Palming, Jenny, 1975, et al.
(författare)
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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
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2346-52
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Tidskriftsartikel (refereegranskat)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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| 13. |
- Sjöholm, Kajsa, 1971, et al.
(författare)
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A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A.
- 2005
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:4, s. 2233-9
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Sjöholm, Kajsa, 1971, et al.
(författare)
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The expression of inhibin beta B is high in human adipocytes, reduced by weight loss, and correlates to factors implicated in metabolic disease.
- 2006
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 344:4, s. 1308-14
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue is an endocrine organ that produces and secretes adipokines. The aim of this study was to identify genes predominantly expressed in human subcutaneous adipocytes. For this purpose, an algorithm was developed and DNA microarray expression profiles from 33 human tissues and cell types were used to select genes. Inhibin beta B (INHBB; coding for the activin betaB subunit) was identified and high expression in adipocytes was confirmed by real-time PCR and immunohistochemistry. INHBB expression in adipose tissue was down regulated by diet-induced weight loss (p<0.001). Furthermore, INHBB expression was positively correlated to total (p<0.001) and subcutaneous (p<0.01) adipose tissue areas and serum levels of fasting insulin (p<0.01) and cholesterol (p<0.05). In conclusion, INHBB expression was high in human adipocytes, reduced by weight loss and adipose tissue INHBB mRNA levels correlated to metabolic risk factors. This suggests that activin B produced in adipocytes may play a role in the metabolic syndrome.
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| 15. |
- Sjöström, Lars, et al.
(författare)
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Effects of bariatric surgery on mortality in Swedish obese subjects.
- 2007
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Ingår i: The New England journal of medicine. - 1533-4406. ; 357:8, s. 741-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. METHODS: The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). RESULTS: The average weight change in control subjects was less than +/-2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29). CONCLUSIONS: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
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