Glucocorticoid metabolism within superficial subcutaneous rather than visceral adipose tissue is associated with features of the metabolic syndrome in South African women

OBJECTIVE: Glucocorticoid hyperactivity in adipose tissue, due to up-regulation of local glucocorticoid reactivation by 11beta-hydroxysteroid dehydrogenase-1 (11HSD1) or of glucocorticoid receptors (GR), may underpin susceptibility to the metabolic syndrome. This hypothesis has been tested extensively in subcutaneous adipose tissue (SAT) but inadequately in visceral adipose tissue (VAT). The aim of the study was therefore to examine expression of 11HSD1, GRalpha and hexose-6-phosphate dehydrogenase (H6PDH), which supplies cofactor for 11HSD1, in abdominal adipose tissue compartments and to characterize their relation to metabolic syndrome parameters. DESIGN AND SUBJECTS: A cross-sectional study including 26 premenopausal South African women. MEASUREMENTS: Biopsies were taken for measurement of mRNA levels by real-time polymerase chain reaction (RT-PCR) and 11HSD1 activity from VAT, and deep and superficial SAT compartments during elective surgery. Prior to surgery, blood pressure, blood lipid profile, body composition [by dual X-ray absorptiometry (DEXA) scan], body fat distribution [by computed tomography (CT) scan], and glucose tolerance were determined. RESULTS: 11HSD1 activity (P < 0.01) was higher in VAT than SAT, but 11HSD1 and GRalpha mRNA levels were not statistically different between compartments. 11HSD1 mRNA levels in superficial SAT correlated with VAT volume (R = 0.57, P < 0.01), insulin sensitivity calculated from the oral glucose tolerance test (OGTT) (R = -0.52, P < 0.016) and blood pressure (R = 0.48, P < 0.016). Apart from a correlation between deep SAT 11HSD1 activity and blood pressure (R = 0.72, P < 0.01), glucocorticoid action in deep SAT and VAT depots was not significantly associated with any metabolic syndrome parameters. CONCLUSION: Increased capacity for glucocorticoid regeneration in superficial SAT but not VAT is associated with visceral adiposity and other features of the metabolic syndrome in women.     

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

BACKGROUND: Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. METHODS: We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. RESULTS: Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. CONCLUSIONS: The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are independent of amounts of VAT or SAT.     

Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study

Visceral adipose tissue (VAT) is an independent risk factor for metabolic and cardiovascular disorders. There has been no study that demonstrated different abdominal fat distribution between Asian and Caucasian men. As the Japanese are less obese but more susceptible to metabolic disorders than Caucasians, they may have larger VAT than Caucasians at similar levels of obesity. We compared the abdominal fat distribution of the Japanese (n=239) and Caucasian-American (n=177) men aged 40-49 years in groups stratified by waist circumference in a population-based sample. We obtained computed tomography images and determined areas of VAT and subcutaneous adipose tissue (SAT). We calculated VAT to SAT ratio (VSR). The Japanese men had a larger VAT and VSR in each stratum, despite substantially less obesity overall. In multiethnic studies, difference in abdominal fat distribution should be considered in exploring factors related to obesity.     

Relationship between vaspin gene expression and abdominal fat distribution of Korean women

Visceral adipose tissue-derived serpin (vaspin) is a novel adipokine that is thought to have insulin-sensitizing effects. We investigated vaspin mRNA expression in abdominal adipose tissue and examined how gene expression related to abdominal fat distribution and metabolic parameters in Korean women. We measured anthropometric variables, metabolic parameters, serum vaspin concentration, and vaspin mRNA expression in abdominal adipose tissue obtained from women who underwent abdominal gynecological surgery and were aged 18-67 years (n = 85). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area were measured in 40 subjects using computed tomography (CT). Vaspin expression was analyzed by real-time quantitative RT-PCR according to abdominal fat distribution. Vaspin mRNA expression was greater in adipocytes than in stroma/vascular cells. In the total subjects, vaspin expression was significantly higher in SAT than in VAT. Vaspin expression in SAT in subcutaneous fat type (VSR ≤ 0.3) was significantly higher than in visceral fat type (VSR > 0.3), although vaspin expression in VAT was similar between subcutaneous and visceral fat type. There was a significant negative correlation between vaspin expression in SAT and VAT area (r = -0.55, p = 0.001). Serum vaspin concentration was significantly correlated with fasting insulin (r = 0.30, p = 0.02), HOMA-IR (r = 0.29, p = 0.02), and the ratio of vaspin expression in VAT to vaspin expression in SAT (r = 0.41, p = 0.04). Vaspin expression in abdominal adipose tissue was adipocyte-specific and vaspin expression in SAT decreased as VAT area increased.     

局部体脂及内分泌脂肪调节激素对瘦素水平的影响

目的　研究中国人非超重、超重及肥胖者瘦素水平与局部体脂、内分泌脂肪调节激素之间的关系。方法　用核磁共振 (MRI)测量 15 0例正常糖耐量的非超重、超重及肥胖者的局部体脂。同时测定瘦素、空腹胰岛素、皮质醇、生长激素、总睾酮、游离睾酮、硫酸去氢表雄酮等内分泌脂肪调节激素。结果　 (1)超重或肥胖者瘦素水平升高 ,女性瘦素水平显著高于男性 ;(2 )体脂对瘦素的影响有性别差异 ,在男性 ,瘦素与腹部皮下脂肪显著相关 (r =0 .75 ,P <0 .0 0 1) ;在女性 ,瘦素与体重指数相关 (r =0 .6 5 ,P <0 .0 0 1) ;(3)胰岛素是独立于体脂之外的调节瘦素的因素 ;(4 )游离睾酮参与瘦素的调节 ,但对瘦素的影响因性别而不同。结论　皮下脂肪是影响瘦素的局部体脂因素 ,胰岛素及雄性激素参与瘦素水平的调节     

The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue

Objective:Hypoadiponectinemia observed in obesity is associated with insulin resistance, diabetes and atherosclerosis. The aim of the present study was to investigate secretion of adiponectin and its multimeric isoforms by explants derived from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese and non-obese subjects.Design:Paired samples of SAT and VAT and blood samples were obtained from 23 subjects (10 non-obese and 13 obese) undergoing elective abdominal surgery. Total adiponectin quantities and adiponectin isoforms were measured in conditioned media of explants derived from SAT and VAT using enzyme-linked immunosorbent assay and non-denaturing western blot, respectively.Results:Total adiponectin plasma levels were lower in obese than in non-obese subjects (P<0.05). Secretion of total adiponectin in adipose tissue (AT) explants was lower in obese than in non-obese subjects in SAT (P<0.05) but not in VAT. In both, SAT and VAT, the most abundant isoform released into conditioned media was the high-molecular weight (HMW) form. Its relative proportion in relation to total adiponectin was higher in conditioned media of explants from both fat depots when compared with plasma (P<0.001). The proportion of secreted HMW vs total adiponectin was higher in VAT than in SAT explants in the group of non-obese individuals (49.3±3.1% in VAT vs 40.6±2.8% in SAT; P<0.01), whereas no difference between the two depots was found in obese subjects (46.2±3.0 % in VAT vs 46.0±2.4 % in SAT).Conclusion:Obesity is associated with the decrease of total adiponectin secretion in SAT. The profile of adiponectin isoforms secreted by SAT and VAT explants differs from that in plasma. Secretion of total adiponectin and HMW isoform of adiponectin are different in obese and non-obese subjects in relation to AT depot.     

Relationship between serum adiponectin and leptin concentrations and body fat distribution

The aim of this study was to investigate the relationship between adiponectin and leptin and body fat distribution. One hundred and ninety-seven women participated in this study. Subjects were grouped based on their visceral adipose tissue area (VAT). Body fat distribution was determined by computed tomography. The numbers in the subcutaneous fat dominant group (SFDG) and visceral fat dominant group (VFDG) were 79 and 118, respectively. The VFDG showed lower adiponectin levels than the SFDG (8.9+/-0.4 microg/ml versus 11.4+/-0.7 microg/ml, P=0.006), but leptin levels did not differ significantly between groups (18.8+/-1.1 ng/ml versus 17.7+/-1.8 ng/ml, P=0.111). Adiponectin levels were inversely correlated with fasting insulin, HOMA-IR, triglyceride, SBP and DBP, subcutaneous adipose tissue area (SAT) and VAT, and waist-to-hip ratio (WHR). Leptin levels were positively correlated with fasting glucose and insulin, HOMA-IR, triglyceride, SBP and DBP, VAT and SAT, and WHR (all values of P<0.05). VAT and HDL-cholesterol were independent variables of adiponectin concentrations (R(2)=0.207, P<0.0001), and SAT, fasting insulin, and HOMA-IR were independent variables of leptin concentrations (R(2)=0.498, P<0.0001) In conclusion, adiponectin and leptin concentrations, although associated with metabolic parameters, were more strongly influenced by VAT in the case of adiponectin, and by SAT in the case of leptin.     

The ratio of visceral to subcutaneous fat, a metric of body fat distribution, is a unique correlate of cardiometabolic risk

Aims/hypothesis  

The anatomic location of excess body fat has an impact on associated cardiometabolic morbidity, and visceral adipose tissue (VAT) is more pathogenic than subcutaneous adipose tissue (SAT). However, VAT or SAT alone provides little information regarding the relative distribution of body fat. We hypothesised that the propensity to store energy in VAT relative to SAT depots may be a correlate of cardiometabolic risk, and tested this hypothesis using the VAT/SAT ratio as a metric of fat distribution.     

Association of abdominal fat distribution and cardiometabolic risk factors among obese Korean adolescents

The association between abdominal fat distribution and cardiometabolic risk factors using direct measures of abdominal fat in adolescents has not been extensively researched. This study was designed to investigate the association between visceral and subcutaneous fat and cardiometabolic risk factors, in obese Korean adolescents. The study enrolled 175 adolescents (72 boys, 103 girls), from ages nine to 19 years, who were referred to the Obesity Clinic of Asan Medical Center. Body mass index (BMI) and waist circumference (WC) were measured for each study participant. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were calculated by computed tomography. Blood pressure, fasting plasma glucose, total cholesterol, triglycerides, HDL cholesterol, insulin and homeostasis model assessment (HOMA) score were measured. Systolic blood pressure, HDL cholesterol, fasting insulin and the HOMA score were significantly correlated with BMI, WC, VAT and SAT. In addition, VAT was significantly correlated with diastolic blood pressure and triglyceride levels. On multiple regression analysis, VAT was independently correlated with blood pressure, triglycerides, HDL cholesterol, fasting insulin and the HOMA score, while SAT was independently correlated with systolic blood pressure, fasting insulin and the HOMA score. This study determined that cardiovascular risk factors are closely associated with VAT, while insulin resistance is closely associated with both VAT and SAT among obese Korean adolescents.     

Modifications of abdominal fat and hepatic insulin clearance during severe caloric restriction

Using computed tomography on 19 obese female subjects, we determined abdominal adipose tissue, both subcutaneous and visceral adipose tissue, before and after 2 weeks of a very low caloric diet (VLCD). The following parameters were also determined before and after 15-20 days of VLCD: plasma glucose and insulin levels, oral glucose tolerance test, basal pancreatic insulin secretion estimated by fasting C peptide (Cp), and fasting insulin hepatic clearance calculated by Cp/insulin molar ratio. After VLCD the body weight and body mass index significantly declined (p less than 0.01); whereas abdominal adipose tissue and visceral abdominal tissue (VAT) significantly decreased (p less than 0.01), modifications of subcutaneous abdominal tissue (SAT) were not significant. Fasting insulin levels and plasma glucose response to oral glucose load significantly decreased (p less than 0.05). Insulin response remained unchanged. Cp immunoreactive insulin (IRI) significantly increased (p less than 0.01). A significant positive correlation was found between delta VAT and delta Cp/IRI before and after VLCD (p less than 0.01). Our data seem to suggest that the weight loss induced by VLCD fundamentally involves a decrease in VAT. The reduction in visceral fat could be associated with an increase in hepatic insulin clearance.     

The morphology and metabolism of intraabdominal adipose tissue in men.

Mass, morphology, and metabolism of total adipose tissue and its subcutaneous, visceral, and retroperitoneal subcompartments were examined in 16 men with a wide variation of total body fat. Computerized tomography (CT) scans showed that the intraabdominal fat mass comprised approximately 20% of total fat mass. Visceral and retroperitoneal fat masses were approximately 80% and 20% of total intraabdominal fat mass, respectively. Enlargement of intraabdominal fat depots was due to a parallel adipocyte enlargement only. Direct significant correlations were found between these adipose tissue masses and blood glucose and plasma insulin levels, blood pressure, and liver function tests, while glucose disposal rate during euglycemic glucose clamp measurements at submaximal insulin concentrations (GDR), plasma testosterone, and sex hormone-binding globulin concentrations correlated negatively. The correlations for glucose, insulin, and GDR were strongest with visceral fat mass. Adipose tissue lipid uptake, measured after oral administration of labeled oleic acid in triglyceride, was approximately 50% higher in omental than in subcutaneous adipose tissues. Adipocytes from omental fat also showed a higher lipolytic sensitivity and responsiveness to catecholamines. Furthermore, these adipocytes were less sensitive to the antilipolytic effects of insulin. Both lipid uptake and lipolytic sensitivity and responsiveness showed strong correlations (r = 0.8 to 0.9) to blood glucose and plasma insulin concentrations and also to the GDR (negative), while no such correlations were found with lipid uptake in subcutaneous or retroperitoneal abdominal adipose tissues. Taken together, these results suggest a higher turnover of lipids in visceral than in the other fat depots, which is closely correlated to systemic insulin resistance and glucose metabolism in men.     

Is the reduction of lower-body subcutaneous adipose tissue associated with elevations in risk factors for diabetes and cardiovascular disease?

AIMS/HYPOTHESIS: Since the accumulation of lower-body subcutaneous adipose tissue (LBSAT) is associated with decreased cardiometabolic risk, we evaluated whether reductions in LBSAT independent of changes in visceral AT (VAT) and abdominal SAT are associated with elevations in diabetes and cardiovascular disease risk factors. METHODS: Overweight and obese men (n = 58) and premenopausal women (n = 49) with elevated cardiometabolic risk underwent 3 months of diet and/or exercise induced weight-loss treatment; regional body composition assessment by magnetic resonance imaging (MRI); and cardiometabolic risk assessment, including an OGTT. RESULTS: After control for potential confounders, reductions in VAT, abdominal SAT and LBSAT were all associated with improvements in selective cardiometabolic risk factors, including fasting glucose levels, lipid status and OGTT glucose and insulin. Independent of changes in the other AT depots, reductions in VAT and abdominal SAT, but not LBSAT, remained associated with improvement in fasting glucose levels, glucose tolerance and lipid status. CONCLUSIONS/INTERPRETATION: Among overweight and obese adults with increased cardiometabolic risk, the selective reduction of LBSAT is not associated with elevations in risk factors for diabetes and cardiovascular disease. Thus, the reduction of excess AT conveys health benefit regardless of origin.     

Effects of androgen therapy on adipose tissue and metabolism in older men

We investigated the effects of oxandrolone on regional fat compartments and markers of metabolism. Thirty-two 60- to 87-yr-old men (body mass index, 28.1 +/- 3.4 kg/m(2)) were randomized to oxandrolone (20 mg/d; n = 20) or matching placebo (n = 12) treatment for 12 wk. Oxandrolone reduced total (-1.8 +/- 1.0 kg; P < 0.001), trunk (-1.2 +/- 0.6 kg; P < 0.001), and appendicular (-0.6 +/- 0.6 kg; P < 0.001) fat, as determined by dual energy x-ray absorptiometry. The changes in total and trunk fat were greater (P < 0.001) than the changes with placebo. By magnetic resonance imaging, visceral adipose tissue decreased (-20.9 +/- 12 cm(2); P < 0.001), abdominal sc adipose tissue (SAT) declined (-10.7 +/- 12.1 cm(2); P = 0.043), the ratio VAT/SAT declined from 0.57 +/- 0.23 to 0.49 +/- 0.19 (P = 0.002), and proximal and distal thigh SC fat declined [-8.3 +/- 6.7 cm(2) (P < 0.001) and -2.2 +/- 3.0 kg (P = 0.004), respectively]. Changes in proximal and distal thigh SC fat with oxandrolone were different than with placebo (P = 0.018 and P = 0.059). A marker of insulin sensitivity (quantitative insulin sensitivity check index) improved with oxandrolone by 0.0041 +/- 0.0071 (P = 0.018) at study wk 12. Changes in total fat, abdominal SAT, and proximal extremity SC fat were correlated with changes in fasting insulin from baseline to study wk 12 (r >or= 0.45; P < 0.05). Losses of total fat and SAT were greater in men with baseline testosterone of 10.4 nmol/liter or less (相似文献   

Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk

Metabolic syndrome is related to multiple cardiovascular risk factors. Visceral adipose tissue (VAT) plays a key role in metabolic syndrome. Easy detection of VAT could be an important tool to increase knowledge of metabolic syndrome. The objective of this study was to study the relationship of echocardiographic epicardial adipose tissue to anthropometric and clinical parameters of metabolic syndrome. We selected 72 consecutive subjects, 46.5 +/- 17.4 yr of age, with a body mass index between 22 and 47 kg/m(2). Each subject underwent transthoracic echocardiogram to measure epicardial fat thickness on right ventricle and magnetic resonance imaging to calculate visceral adipose tissue. Anthropometric, metabolic, and cardiac parameters were also evaluated. Echocardiographic epicardial adipose tissue showed a very good correlation with magnetic resonance imaging abdominal VAT and epicardial fat measurement (Bland-Altman plot and linear regression). Multiple regression analysis showed that waist circumference (r(2) = 0.428; P = 0.01), diastolic blood pressure (r(2) = 0. 387; P = 0.02), and fasting insulin (r(2) = 0.387; P = 0.03) were the strongest independent variables correlated with epicardial adipose tissue. Echocardiographic epicardial adipose tissue could be applied as an easy and reliable imaging indicator of VAT and cardiovascular risk.     

Relationship of visceral adipose tissue to metabolic risk factors for coronary heart disease: is there a contribution of subcutaneous fat cell hypertrophy?

Visceral adipose tissue (VAT) accumulation is an important correlate of the metabolic complications found in obese patients. The aim of this study was to evaluate the respective contribution of VAT deposition versus subcutaneous abdominal or femoral fat cell hypertrophy as correlates of the metabolic risk profile in 69 men and 65 premenopausal women (aged 35+/-5 years) with a wide range of fatness (body mass index, 18 to 57 kg/m2). In both genders, VAT accumulation was positively correlated with fasting plasma insulin, triglyceride (TG), and low-density lipoprotein (LDL)-apolipoprotein B (apo B) levels and the cholesterol (CHOL)/high-density lipoprotein (HDL)-CHOL ratio (.24 < or = r < or = .71, P < .05). A similar pattern of positive relationships was found between subcutaneous abdominal fat cell weight and metabolic risk variables in men and women (.33 < or = r < or = .60, P < .01). Positive associations were also observed in women between femoral fat cell weight and fasting plasma insulin, TG, and CHOL levels and the CHOL/HDL-CHOL ratio (.29 < or = r < or = .42, P < .05). However, only plasma TG concentrations and the CHOL/HDL-CHOL ratio were positively correlated with femoral fat cell weight in men (r = .30, P < .05). To better investigate the relationships between the metabolic risk profile and hypertrophic subcutaneous obesity, individuals with small versus large subcutaneous abdominal adipocytes were matched according to VAT accumulation. Men with large abdominal fat cells displayed higher plasma TG and LDL-apo B levels compared with men characterized by small abdominal adipocytes (P < .05). Stepwise multiple regression analyses showed that subcutaneous abdominal fat cell weight was the best independent variable predicting plasma TG and LDL-apo B levels in men. No significant difference was found in the metabolic profile of subjects displaying small versus large femoral adipocytes. Taken together, these results suggest that for a given VAT deposition, the presence of hypertrophied subcutaneous abdominal adipocytes in men appears to be associated with further deterioration in the metabolic risk profile. On the other hand, the hypertrophy of femoral adipocytes does not further alter the metabolic complications generally related to obesity in both men and women.     

The relationship of visfatin/pre-B-cell colony-enhancing factor/nicotinamide phosphoribosyltransferase in adipose tissue with inflammation, insulin resistance, and plasma lipids

Visfatin/pre-B-cell colony-enhancing factor (PBEF)/nicotinamide phosphoribosyltransferase (Nampt) has been proposed as an insulin-mimicking adipocytokine predominantly secreted from visceral adipose tissue (VAT) and correlated with obesity. However, recent evidence challenged this proposal and instead suggested visfatin/PBEF/Nampt as a proinflammatory cytokine. The study aimed to examine whether visfatin/PBEF/Nampt was predominantly expressed in VAT and was correlated with obesity. The relationship of visfatin/PBEF/Nampt gene expression in adipose tissues with proinflammatory gene expression and metabolic phenotypes was also examined. The relative messenger RNA (mRNA) levels of visfatin/PBEF/Nampt, macrophage-specific marker CD68, and proinflammatory genes were measured in paired abdominal VAT and subcutaneous adipose tissues (SAT) and from 53 nondiabetic adults using quantitative real-time polymerase chain reaction. Fasting glucose, insulin, triglyceride, cholesterol, and uric acid levels were measured; and systemic insulin sensitivity was quantified with modified insulin suppression tests. There was no difference in visfatin/PBEF/Nampt mRNA levels between VAT and SAT, and neither was associated with measures of obesity. Visfatin/PBEF/Nampt mRNA levels were strongly correlated with proinflammatory gene expression including CD68 and tumor necrosis factor-α gene in both VAT and SAT. The VAT and SAT visfatin/PBEF/Nampt mRNA expressions were positively correlated with steady-state plasma glucose concentrations measured with modified insulin suppression tests, a direct measurement of systemic insulin resistance (r = 0.42, P = .03 and r = 0.44, P = .03, respectively). The VAT visfatin/PBEF/Nampt mRNA expression was also positively correlated with fasting triglyceride (r = 0.42, P = .002) and total cholesterol levels (r = 0.37, P = .009). Visfatin/PBEF/Nampt is not predominantly secreted from VAT and is not correlated with obesity. Our findings suggest that visfatin/PBEF/Nampt is a proinflammatory marker of adipose tissue associated with systemic insulin resistance and hyperlipidemia.     

Association between low SIRT1 expression in visceral and subcutaneous adipose tissues and metabolic abnormalities in women with obesity and type 2 diabetes

Aims

To assess the importance of adipose tissue sirtuin 1 (SIRT1) in the regulation of whole-body metabolism in humans with obesity and type 2 diabetes.

Methods

In total, 19 non-diabetic obese women, 19 type 2 diabetic women undergoing gastric bypass surgery, and 27 normal-weight women undergoing gynecological surgery (total 65 women) were enrolled. Their anthropometric variables, abdominal fat distribution and metabolic parameters, serum adiponectin concentrations, and SIRT1 mRNA and protein and adiponectin mRNA expressions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured.

Results

SIRT1 mRNA levels in VAT and SAT were similar and these levels were suppressed in obese and type 2 diabetic women compared to normal-weight subjects. These decreases in SIRT1 expression were observed in both adipocytes and non-fat cells. There was a strong association between adipose tissue SIRT1 mRNA and protein levels. Adipose SIRT1 expression correlated inversely with HOMA-IR and other insulin resistance-related parameters. Adipose SIRT1 and adiponectin mRNA expression correlated very strongly and positively. SIRT1 mRNA level in VAT correlated inversely with visceral obesity whereas its expression in SAT correlated negatively with body mass index.

Conclusions

Adipose tissue SIRT1 may play a key role in the regulation of whole body metabolic homeostasis in humans. Downregulation of SIRT1 in VAT may contribute to the metabolic abnormalities that are associated with visceral obesity.     

Regional similarities in the metabolic regulation of adipose tissue lipoprotein lipase.

Seven normal weight and 10 obese women were studied to determine the relative activities of adipose tissue lipoprotein lipase (ATLPL) in the gluteal and abdominal subcutaneous adipose tissue depots, both in the fasting state and in response to a 6-hour insulin/glucose infusion. In normal weight women, fasting gluteal enzyme activity was greater than abdominal (P less than .02). In the obese group, fasting levels of ATLPL were higher in both the gluteal and abdominal depots than in the normal weight group, but similar between regions. The regulation of ATLPL by insulin/glucose was also similar between regions in each group. When both groups were considered together, there was a strong correlation between fasting ATLPL of both regions, and between the insulin responsiveness of gluteal ATLPL and abdominal ATLPL after a 6-hour infusion. Despite regional differences in fasting ATLPL in lean women, these studies indicate that the regulation of ATLPL by insulin/glucose is largely similar in at least these two subcutaneous adipose tissue depots.     

Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight ( approximately 4.5 kg) and percent body fat ( approximately 5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat ( approximately 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.