Association of Pericardial Fat With Liver Fat and Insulin Sensitivity After Diet‐Induced Weight Loss in Overweight Women

Pericardial adipose tissue (PAT) is positively associated with fatty liver and obesity‐related insulin resistance. Because PAT is a well‐known marker of visceral adiposity, we investigated the impact of weight loss on PAT and its relationship with liver fat and insulin sensitivity independently of body fat distribution. Thirty overweight nondiabetic women (BMI 28.2–46.8 kg/m², 22–41 years) followed a 14.2 ± 4‐weeks low‐calorie diet. PAT, abdominal subcutaneous (SAT), and visceral fat volumes (VAT) were measured by magnetic resonance imaging (MRI), total fat mass, trunk, and leg fat by dual‐energy X‐ray absorptiometry and intrahepatocellular lipids (IHCL) by (¹)H‐magnetic resonance spectroscopy. Euglycemic hyperinsulinemic clamp (M) and homeostasis model assessment of insulin resistance (HOMA_IR) were used to assess insulin sensitivity or insulin resistance. At baseline, PAT correlated with VAT (r = 0.82; P < 0.001), IHCL (r = 0.46), HOMA_IR (r = 0.46), and M value (r = ?0.40; all P < 0.05). During intervention, body weight decreased by ?8.5%, accompanied by decreases of ?12% PAT, ?13% VAT, ?44% IHCL, ?10% HOMA2‐%B, and +24% as well as +15% increases in HOMA2‐%S and M, respectively. Decreases in PAT were only correlated with baseline PAT and the loss in VAT (r = ?0.56; P < 0.01; r = 0.42; P < 0.05) but no associations with liver fat or indexes of insulin sensitivity were observed. Improvements in HOMA_IR and HOMA2‐%B were only related to the decrease in IHCL (r = 0.62, P < 0.01; r = 0.65, P = 0.002) and decreases in IHCL only correlated with the decrease in VAT (r = 0.61, P = 0.004). In conclusion, cross‐sectionally PAT is correlated with VAT, liver fat, and insulin resistance. Longitudinally, the association between PAT and insulin resistance was lost suggesting no causal relationship between the two.     

Serum Leptin in Elderly People: Associations with Sex Hormones,Insulin, and Adipose Tissue Volumes

BAUMGARTNER, RICHARD N., ROBERT R. ROSS, DEBRA L. WATERS, WILLIAM M. BROOKS, JOHN E. MORLEY, GEORGE D. MONTOYA, AND PHILIP J. GARRY. Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes Res. Objective There are few data for associations of serum leptin with body fat, fat distribution, sex hormones, or fasting insulin in elderly adults. We hypothesized that the sex difference in serum leptin concentrations would disappear after adjustment for subcutaneous, but not visceral body fat. Serum leptin would not be associated with sex hormone concentrations or serum fasting insulin after adjusting for body fat and fat distribution. Research Methods and Procedures Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured using magnetic resonance imaging in a cross-sectional sample of 56 nondiabetic, elderly men and women aged 64 years to 94 years. Serum leptin, sex hormones (testosterone and estrone), sex hormone-binding globulin, and fasting insulin were also measured. Nine women were taking hormone replacement, and five men were clinically hypogonadal. Results Leptin was significantly associated with both SAT and VAT in each sex. Adjustment for SAT reduced the sex difference in leptin by 56%, but adjustment for VAT increased the difference by 25%. Leptin was not associated with serum estrone or hormone replacement therapy in the women, but had a significant, negative association with testosterone in the men that was independent of SAT, but not VAT. Leptin was significantly associated with fasting insulin in both sexes independent of age, sex hormones, sex hormone-binding globulin, VAT and SAT. Discussion Sex difference in serum leptin is partly explained by different amounts of SAT. Studies including both men and women should adjust for SAT rather than total body fat that includes VAT. The sex difference in serum leptin is not due to estrogen, but may be partly explained by testosterone. Testosterone is negatively associated with leptin in men, but the association is confounded with VAT. Leptin is associated with fasting insulin in non-diabetic elderly men and women independent of body fat, fat distribution. or sex hormones.     

Deep subcutaneous adipose tissue: a distinct abdominal adipose depot

Objective: Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) display significant metabolic differences, with VAT showing a functional association to metabolic/cardiovascular disorders. A third abdominal adipose layer, derived by the division of SAT and identified as deep subcutaneous adipose tissue (dSAT), may play a significant and independent metabolic role. The aim of this study was to evaluate depot‐specific differences in the expression of proteins key to adipocyte metabolism in a lean population to establish a potential physiologic role for dSAT. Research Methods and Procedures: Adipocytes and preadipocytes were isolated from whole biopsies taken from superficial SAT (sSAT), dSAT, and VAT samples obtained from 10 healthy normal weight patients (7 women and 3 men), with a mean age of 56.4 ± 4.04 years and a mean BMI of 23.1 ± 0.5 kg/m². Samples were evaluated for depot‐specific differences in insulin sensitivity using adiponectin, glucose transport protein 4 (GLUT4), and resistin mRNA and protein expression, glucocorticoid metabolism by 11β‐hydroxysteroid dehydrogenase type‐1 (11β‐HSD1) expression, and alterations in the adipokines leptin and tumor necrosis factor‐α (TNF‐α). Results: Although no regional differences in expression were observed for adiponectin or TNF‐α, dSAT whole biopsies and adipocytes, while intermediary to both sSAT and VAT, reflected more of the VAT expression profile of 11β‐HSD1, leptin, and resistin. Only in the case of the intracellular pool of GLUT4 proteins in whole biopsies was an independent pattern of expression observed for dSAT. In an evaluation of the homeostatic model, dSAT 11β‐HSD1 protein (r = 0.9573, p = 0.0002) and TNF‐α mRNA (r = 0.8210, p = 0.0236) correlated positively to the homeostatic model. Discussion: Overall, dSAT seems to be a distinct abdominal adipose depot supporting an independent metabolic function that may have a potential role in the development of obesity‐associated complications.     

Dual‐energy X‐ray Absorptiometry and Anthropometric Estimates of Visceral Fat in Black and White South African Women

Visceral adipose tissue (VAT) is associated with increased risk for cardiovascular disease, and therefore, accurate methods to estimate VAT have been investigated. Computerized tomography (CT) is the gold standard measure of VAT, but its use is limited. We therefore compared waist measures and two dual‐energy X‐ray absorptiometry (DXA) methods (Ley and Lunar) that quantify abdominal regions of interest (ROIs) to CT‐derived VAT in 166 black and 143 white South African women. Anthropometry, DXA ROI, and VAT (CT at L4–L5) were measured. Black women were younger (P < 0.001), shorter (P < 0.001), and had higher body fat (P < 0.05) than white women. There were no ethnic differences in waist (89.7 ± 18.2 cm vs. 90.1 ± 15.6 cm), waist:height ratio (WHtR, 0.56 ± 0.12 vs. 0.54 ± 0.09), or DXA ROI (Ley: 2.2 ± 1.5 vs. 2.1 ± 1.4; Lunar: 2.3 ± 1.4 vs. 2.3 ± 1.5), but black women had less VAT, after adjusting for age, height, weight, and fat mass (76 ± 34 cm² vs. 98 ± 35 cm²; P < 0.001). Ley ROI and Lunar ROI were correlated in black (r = 0.983) and white (r = 0.988) women. VAT correlated with DXA ROI (Ley: r = 0.729 and r = 0.838, P < 0.01; Lunar: r = 0.739 and r = 0.847, P < 0.01) in black and white women, but with increasing ROI android fatness, black women had less VAT. Similarly, VAT was associated with waist (r = 0.732 and r = 0.836, P < 0.01) and WHtR (r = 0.721 and r = 0.824, P < 0.01) in black and white women. In conclusion, although DXA‐derived ROIs correlate well with VAT as measured by CT, they are no better than waist or WHtR. Neither DXA nor anthropometric measures are able to accurately distinguish between high and low levels of VAT between population groups.     

Differential Effects of Abdominal Adipose Tissue Distribution on Insulin Sensitivity in Black and White South African Women

Black South African women are more insulin resistant than BMI‐matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal‐weight (BMI 18–25 kg/m²) and obese (BMI > 30 kg/m²) black and white premenopausal South African women underwent the following measurements: body composition (dual‐energy X‐ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (S_I, frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 ± 0.8 vs. 9.5 ± 0.8 and 3.0 ± 0.8 vs. 6.0 ± 0.8 × 10^?5/min/(pmol/l), for normal‐weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. S_I correlated with deep and superficial SAT in both black (R = ?0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = ?0.554, P = 0.005 and R = ?0.546, P = 0.004), but with VAT in white women only (R = ?0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.     

Impacts of Visceral Adipose Tissue and Subcutaneous Adipose Tissue on Metabolic Risk Factors in Middle‐aged Japanese

Regional fat distribution rather than overall fat volume has been considered to be important to understanding the link between obesity and metabolic disorders. We aimed to evaluate the independent associations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with metabolic risk factors in apparently healthy middle‐aged Japanese. Participants were 1,119 men and 854 women aged 38–60 years who were not taking medications for diabetes, hypertension, or dyslipidemia. VAT and SAT were measured by use of computed tomography (CT) scanning. VAT and SAT were significantly and positively correlated with each other in men (r = 0.531, P < 0.001) and women (r = 0.589, P < 0.001). In multiple regression analyses, either measure of abdominal adiposity (VAT or SAT) was positively associated with blood pressure, fasting plasma glucose, and log triglyceride (P < 0.001) and inversely with high‐density lipoprotein (HDL)‐cholesterol (P < 0.001). When VAT and SAT were simultaneously included in the model, the association of VAT with triglycerides was maintained (P < 0.001) but that of SAT was lost. The same was true for HDL‐cholesterol in women. For fasting plasma glucose, the association with VAT was strong (P < 0.001) and the borderline association with SAT was maintained (P = 0.060 in men and P = 0.020 in women). Both VAT and SAT were independently associated with blood pressure (P < 0.001). Further adjustment for anthropometric indices resulted in the independent association only with VAT for all risk factors. In conclusion, impacts of VAT and SAT differed among risk factors. VAT showed dominant impacts on triglyceride concentrations in both genders and on HDL‐cholesterol in women, while SAT also had an independent association with blood pressure.     

Plasma Adiponectin Levels Are Not Associated with Fat Oxidation in Humans

Objective: To test the hypothesis that low adiponectin is associated with low fat oxidation in humans. Research Methods and Procedures: We measured plasma adiponectin concentrations in 75 healthy, nondiabetic Pima Indians (age, 28 ± 7 years; 55 men and 20 women; body fat, 29.7 ± 7.5%) and 18 whites [(age, 33 ± 8 years; 14 men and 4 women; body fat, 28.2 ± 10.8% (means ± SD)] whose body composition was measured by DXA and 24-hour energy expenditure (24-hour EE) by a respiratory chamber. Respiratory quotient (an estimate of whole-body carbohydrate/lipid oxidation rate) was calculated over 24 hours (24-hour RQ). Results: Before correlational analyses, waist-to-thigh ratio (WTR) and percentage of body fat (PFAT) were adjusted for age, sex, and race; 24-hour EE was adjusted for fat mass and fat-free mass, and 24-hour RQ were adjusted for energy balance. Plasma adiponectin concentrations were negatively correlated with WTR (r = −0.42, p < 0.0001) and PFAT (r = −0.46, p < 0.0001). There was no correlation between plasma adiponectin concentrations and 24-hour RQ, (r = 0.09, p = 0.36) before or after adjustment for PFAT (r = 0.001, p = 0.99, respectively, partial correlation), and no correlation was found between plasma adiponectin concentrations and 24-hour EE (r = −0.12, p = 0.27). Discussion: Our cross-sectional data do not suggest physiological concentrations of fasting plasma adiponectin play a role in the regulation of whole-body fat oxidation or energy expenditure in resting conditions. Whether administration of adiponectin to individuals with low levels of this hormone will increase their fat oxidation rates/energy expenditure remains to be established.     

Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults

Objective : Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population‐based cohort of obese adults. Design and Methods : Among obese participants in the Dallas Heart Study, we examined the cross‐sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index. Results : In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA‐IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C‐reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA‐IR were significant in univariable analyses but attenuated after multivariable adjustment. Conclusion : VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub‐phenotypes with heterogeneous metabolic and atherosclerosis risk.     

A Single mri Slice Does Not Accurately Predict Visceral and Subcutaneous Adipose Tissue Changes During Weight Loss

Earlier cross‐sectional studies found that a single magnetic resonance imaging (MRI) slice predicts total visceral and subcutaneous adipose tissue (VAT and SAT) volumes well. We sought to investigate the accuracy of trunk single slice imaging in estimating changes of total VAT and SAT volume in 123 overweight and obese subjects who were enrolled in a 24‐week CB‐1R inverse agonist clinical trial (weight change, ?7.7 ± 5.3 kg; SAT change, ?5.4 ± 4.9 l, VAT change, ?0.8 ± 1.0 l). VAT and SAT volumes at baseline and 24 weeks were derived from whole‐body MRI images. The VAT area 5–10 cm above L₄—L₅ (A_+5–10) (R² = 0.59–0.70, P < 0.001) best predicted changes in VAT volume but the strength of these correlations was significantly lower than those at baseline (R² = 0.85–0.90, P < 0.001). Furthermore, the L₄—L₅ slice poorly predicted VAT volume changes (R² = 0.24–0.29, P < 0.001). Studies will require 44–69% more subjects if (A_+5–10) is used and 243–320% more subjects if the L₄—L₅ slice is used for equivalent power of multislice total volume measurements of VAT changes. Similarly, single slice imaging predicts SAT loss less well than cross‐sectional SAT (R² = 0.31–0.49 vs. R² = 0.52–0.68, P < 0.05). Results were the same when examined in men and women separately. A single MRI slice 5–10 cm above L₄—L₅ is more powerful than the traditionally used L₄—L₅ slice in detecting VAT changes, but in general single slice imaging poorly predicts VAT and SAT changes during weight loss. For certain study designs, multislice imaging may be more cost‐effective than single slice imaging in detecting changes for VAT and SAT.     

Fat Depot‐specific Impact of Visceral Obesity on Adipocyte Adiponectin Release in Women

Our objective was to examine omental and subcutaneous adipocyte adiponectin release in women. We tested the hypothesis that adiponectin release would be reduced to a greater extent in omental than in subcutaneous adipocytes of women with visceral obesity. Omental and subcutaneous adipose tissue samples were obtained from 52 women undergoing abdominal hysterectomies (age: 47.1 ± 4.8 years; BMI: 26.7 ± 4.7 kg/m²). Adipocytes were isolated and their adiponectin release in the medium was measured over 2 h. Measures of body fat accumulation and distribution were obtained using dual‐energy X‐ray absorptiometry and computed tomography, respectively. Adiponectin release by omental and subcutaneous adipocytes was similar in lean individuals; however, in subsamples of obese or visceral obese women, adiponectin release by omental adipocytes was significantly reduced while that of subcutaneous adipocytes was not affected. Omental adipocyte adiponectin release was significantly and negatively correlated with total body fat mass (r = ?0.47, P < 0.01), visceral adipose tissue area (r = ?0.50, P < 0.01), omental adipocyte diameter (r = ?0.43, P < 0.01), triglyceride levels (r = ?0.32, P ≤ 0.05), cholesterol/high‐density lipoprotein (HDL)‐cholesterol (r = ?0.31, P ≤ 0.05), fasting glucose (r = ?0.39, P ≤ 0.01), fasting insulin (r = ?0.36, P ≤ 0.05), homeostasis model assessment index (r = ?0.39, P ≤ 0.01), and positively associated with HDL‐cholesterol concentrations (r = 0.33, P ≤ 0.05). Adiponectin release from subcutaneous cells was not associated with any measure of adiposity, lipid profile, or glucose homeostasis. In conclusion, compared to subcutaneous adipocyte adiponectin release, omental adipocyte adiponectin release is reduced to a greater extent in visceral obese women and better predicts obesity‐associated metabolic abnormalities.     

Visceral and Subcutaneous Adiposity and Adiponectin in Middle‐aged Japanese Men: The ERA JUMP Study

Adiponectin is reduced in obesity and has been suggested to play an important role in modulation of atherosclerosis. We studied the relationship between visceral (VAT) and subcutaneous (SAT) adipose tissue and serum adiponectin concentrations in Japanese men. Participants were 304 randomly selected community-based Japanese men aged 40–49 without a prior history of cardiovascular disease. Participants were grouped according to tertiles of serum adiponectin. In multiple linear regression analysis including age, pack years of smoking, and alcohol intake as covariates, log-transformed adiponectin was inversely associated with both VAT and SAT when these two obesity measures were included separately in the models. However, log-transformed adiponectin was inversely associated with VAT (standardized β estimate = −0.465; P < 0.0001) and positively associated with SAT (standardized β estimate = 1.277; P = 0.03), when these were included concomitantly in the model. In conclusion, VAT and SAT had differential associations with serum adiponectin concentrations.     

High visceral fat mass and high liver fat are associated with resistance to lifestyle intervention

Objective: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention. Research Methods and Procedures: One hundred twelve subjects (48 men and 64 women; age, 46 ± 11 years; BMI, 29.2 ± 4.4 kg/m²) were studied after a follow up‐time of 264 ± 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy. Results: Cross‐sectionally high VAT (r = ?0.22, p = 0.02) and high LF (r = ?0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (?3.0%), VAT (?12.0%), and LF (?33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = ?0.41), VAT (r = ?0.28), and LF (r = ?0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = ?0.28, p = 0.01) and high LF (r = ?0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity. Discussion: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.     

Loss of Total and Visceral Adipose Tissue Mass Predicts Decreases in Oxidative Stress After Weight‐loss Surgery

It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 ± 0.8 kg/m² to 43.3 ± 0.8 kg/m² (1 month), 35.2 ± 0.8 kg/m² (6 months), and 30.2 ± 1.2 kg/m² (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6‐month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6‐month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high‐density lipoprotein (HDL) at 1 and 6 months after surgery (r = ?0.38 and ?0.42). This study found longitudinal associations between general, and more specifically intra‐abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.     

Plasma visfatin concentration as a surrogate marker for visceral fat accumulation in obese children

Objective: This study was designed to elucidate whether the plasma visfatin level reflects visceral or subcutaneous fat accumulation and metabolic derangement in obese children. Methods and Procedures: Fifty‐six obese Japanese children, including 37 boys and 19 girls were enrolled in the study. The age of the subjects ranged from 5 to 15 (10.2 ± 0.3; mean ± s.e.m.) years. The age‐matched control group for measuring visfatin consisted of 20 non‐obese children. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by computed tomography. The plasma concentrations for visfatin and leptin were assayed by enzyme‐linked immunosorbent assay kits. Results: The plasma visfatin level was higher in the obese (14.7 ± 0.9 ng/ml) than in the control children (8.6 ± 0.6 ng/ml). In a univariate analysis, the visfatin correlated significantly with age, height, body weight, waist circumference, VAT and SAT area, triglyceride (TG), insulin, and the homeostasis model assessment for insulin resistance (HOMA‐R). After being adjusted for age and sex, only the VAT area retained significant partial correlation with visfatin, and in contrast the body weight, BMI–s.d., and SAT area with leptin. The plasma visfatin concentration was not correlated with leptin. The plasma visfatin levels in the control, non‐metabolic syndrome (MS) (n = 49), and MS groups (n = 7) were significantly different from each other. Discussion: These results suggest that plasma visfatin level is a specific marker for visceral fat accumulation in obese children. As a good surrogate marker, plasma visfatin level can predict the VAT area in obese children.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Both Subcutaneous and Visceral Adipose Tissue Correlate Highly with Insulin Resistance in African Americans

Objective: The contribution of visceral adipose tissue (VAT) to insulin resistance is well‐established; however, the role of subcutaneous abdominal adipose tissue (SAT) in insulin resistance remains controversial. Sex may determine which of these two components of abdominal obesity is more strongly related to insulin resistance and its consequences. The aim of this study was to determine whether both VAT and SAT contribute to insulin resistance in African Americans and to examine the effects of sex on this relationship. Research Methods and Procedures: This was a cross‐sectional study of 78 nondiabetic African‐American volunteers (44 men, 35 women; age 33.8 ± 7.3 years; BMI 30.9 ± 7.4 kg/m²). VAT and SAT volumes were measured using serial computerized tomography slices from the dome of the diaphragm to the iliac crest. The insulin sensitivity index (S_I) was determined from the minimal model using data obtained from the frequently sampled intravenous glucose tolerance test. Results: In men, both VAT and SAT were negatively correlated with S_I (r for both correlations = ?0.57; p < 0.01). In women, the correlation coefficient between VAT and S_I was ?0.50 (p < 0.01) and between SAT and S_I was ?0.67 (p < 0.01). In women, the correlation coefficient for S_I with SAT was significantly greater than the correlation coefficient with VAT (p = 0.02). Discussion: Both SAT and VAT are strongly correlated with insulin resistance in African Americans. For African‐American women, SAT may have a greater effect than VAT on insulin resistance.     

Comparison of Regional Fat Distribution and Health Risk Factors in Middle‐Aged White and African American Women: The Healthy Transitions Study

Objective: Both ethnicity and menopause appear to influence intra‐abdominal fat distribution. This study evaluated intra‐abdominal fat distribution and obesity‐related health risks in perimenopausal white and African American women. Research Methods and Procedures: Baseline data from a longitudinal study of changes in body composition and energy balance during menopause are reported. Healthy women (55 African Americans and 103 whites) who were on no medication and had at least five menstrual cycles in the previous 6 months were recruited. Body composition was assessed by DXA, and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography scan. SAT was divided into deep and superficial layers demarcated by the fascia superficialis. Results: African American women were slightly younger (46.7 ± 0.2 vs. 47.7 ± 0.2 years, p = 0.002) and fatter (42.4% ± 1.0% vs. 39.4% ± 0.8% body fat, p = 0.02) than white women. In unadjusted data, African Americans had significantly more total abdominal fat and total, deep, and superficial SAT than whites. After adjustment for percent body fat and age, only total and superficial SAT remained significantly higher in African Americans. VAT although slightly less in African American women, did not differ significantly by race. In multiple regression analysis, VAT was the strongest predictor of serum lipids, glucose, and insulin in women of both races, although superficial SAT was significantly associated with fasting glucose in whites. Conclusions: Middle‐aged African American women have larger SAT depots, adjusted for total body fatness, but do not differ from white women with regard to VAT. The complexity of the relationship between abdominal fat and metabolic risk is increased by ethnic differences in such associations.     

Relationship of Intramyocellular Lipid to Insulin Sensitivity May Differ With Ethnicity in Healthy Girls and Women

The prevalence of type 2 diabetes is greater among African Americans (AA) vs. European Americans (EA), independent of obesity and lifestyle. We tested the hypothesis that intramyocellular lipid (IMCL) or extramycellular lipid (EMCL) would be associated with insulin sensitivity among healthy young women, and that the associations would differ with ethnic background. We also explored the hypothesis that adipokines and estradiol would be associated with muscle lipid content. Participants were 57 healthy, normoglycemic, women and girls mean age 26 (±10) years; mean BMI 27.3 (±4.8) kg/m²; 32 AA, 25 EA. Soleus IMCL and EMCL were assessed with ¹H magnetic resonance spectroscopy (MRS); insulin sensitivity with an insulin‐modified frequently sampled intravenous glucose tolerance test and minimal modeling; body composition with dual‐energy X‐ray absorptiometry; and intra‐abdominal adipose tissue (IAAT) with computed tomography. Adiponectin, leptin, and estradiol were assessed in fasting sera. Analyses indicated that EMCL, but not IMCL, was greater in AA vs. EA (2.55 ± 0.16 vs. 1.98 ± 0.18 arbitrary units, respectively, P < 0.05; adjusted for total body fat). IMCL was associated with insulin sensitivity in EA (r = ?0.54, P < 0.05, adjusted for total fat, IAAT, and age), but not AA (r = 0.16, P = 0.424). IMCL was inversely associated with adiponectin (r = ?0.31, P < 0.05, adjusted for ethnicity, age, total fat, and IAAT). In conclusion, IMCL was a significant determinant of insulin sensitivity among healthy, young, EA but not AA women. Further research is needed to determine whether the component lipids of IMCL (e.g., diacylglycerol (DAG) or ceramide) are associated with insulin sensitivity in an ethnicity specific manner.     

In Utero Gender Dimorphism of Adiponectin Reflects Insulin Sensitivity and Adiposity of the Fetus

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin‐sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. To further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition, and gender. Umbilical cord adiponectin, adiponectin complexes, and metabolic parameters were measured at term by elective cesarean delivery. The associations between adiponectin, measures of body composition, and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in female compared with male fetuses (34.3 ± 9.5 vs. 24.9 ± 8.6, P < 0.001) were associated with a 3.2‐fold greater abundance in circulating HMW complexes (0.20 ± 0.03 vs. 0.08 ± 0.03, P < 0.001, n = 9). Adiponectin was positively correlated with neonatal fat mass (r = 0.27, P < 0.04) and percent body fat in female fetuses (r = 0.28, P < 0.03) and with lean mass in males (r = 0.28, P < 0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.     

Epicardial Fat from Echocardiography: A New Method for Visceral Adipose Tissue Prediction

Objective: To validate transthoracic echocardiography as an easy and reliable imaging method for visceral adipose tissue (VAT) prediction. VAT is recognized as an important indicator of high cardiovascular and metabolic risk. Several methods are applied to estimate VAT, with different results. Research Methods and Procedures: We selected 60 healthy subjects (29 women, 31 men, 49.5 ± 16.2 years) with a wide range of body mass indexes. Each subject underwent transthoracic echocardiogram and magnetic resonance imaging (MRI) to measure epicardial fat thickness on the right ventricle. Measurements of epicardial adipose tissue thickness were obtained from the same echocardiographic and MRI views and points. MRI was also used to measure VAT cross‐sectional areas at the level of L4 to L5. Anthropometric indexes were also measured. Results: Subjects with predominant visceral fat accumulation showed higher epicardial adipose tissue thickness than subjects with predominant peripheral fat distribution: 9.97 ± 2.88 vs. 4.34 ± 1.98 (p = 0.005) and 7.19 ± 2.74 vs. 3.43 ± 1.64 (p = 0.004) in men and women, respectively. Simple linear regression analysis showed an excellent correlation between epicardial adipose tissue and waist circumference (r = 0.895, p = 0.01) and MRI abdominal VAT (r = 0.864, p = 0.01). Multiple regression analysis showed that epicardial adipose tissue thickness (r² = 0.442, p = 0.02) was the strongest independent variable correlated to MRI VAT. Bland test confirmed the good agreement between the two methods. Discussion: Epicardial adipose tissue showed a strong correlation with anthropometric and imaging measurements of VAT. Hence, transthoracic echocardiography could be an easy and reliable imaging method for VAT prediction.