Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk

There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the "metabolic syndrome" or by others "syndrome X" or "insulin resistance syndrome", it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal obesity and the metabolic syndrome, such global risk being defined as cardiometabolic risk.     

Abdominal Obesity and Cardiovascular Disease: Is Inflammation the Missing Link?

It is well established that cardiovascular disease has an inflammatory component. The present narrative review explores the role of adipose tissue distribution, morphology, and function as potential mediators of the link between inflammation and cardiovascular disease. Evidence that abdominal obesity is a key driving force behind a constellation of atherothrombotic inflammatory abnormalities linked to insulin resistance and often referred to as the metabolic syndrome is also reviewed. It is also proposed that the amount of visceral adipose tissue and the liver fat content are important factors responsible for the link between abdominal obesity and features of the metabolic syndrome. It is suggested that the inflammatory profile associated with excess visceral adipose tissue/liver fat may be a consequence of the relative inability of subcutaneous adipose tissue to expand through hyperplasia and to act as a protective metabolic sink storing the chronic energy surplus resulting from a positive energy balance (overnutrition or lack of physical activity or both). In this model, the inflammatory profile often observed among sedentary overweight/obese individuals with an excess of visceral adipose tissue/liver fat may be a consequence of a more primary defect in subcutaneous adipose tissue. On that basis, it is proposed that therapeutic strategies relieving the stress for storage of a chronic energy surplus in the subcutaneous adipose tissue (reduced caloric intake, increase in energy expenditure, pharmacotherapy) should induce a substantial loss of visceral adipose tissue and of ectopic fat depots such as the liver, thereby substantially reducing inflammation.     

Chemerin levels are positively correlated with abdominal visceral fat accumulation

Objective Chemerin, a recently discovered adipocytokine, may be linked to obesity and obesity‐associated metabolic complications. However, the relationship between visceral fat accumulation and chemerin is still unknown. Therefore, we investigated the relationship between serum chemerin levels and body composition as measured by computed tomography (CT). Patients We recruited 173 men and women without histories of diabetes or cardiovascular disease. Measurements Biomarkers of metabolic risk factors and body composition by computed tomography were assessed. Serum chemerin levels were measured by enzyme‐linked immunosorbent assay. Results Chemerin levels correlated with body mass index (BMI), waist circumference, abdominal visceral fat area, blood pressure, fasting insulin, homoeostasis model of assessment‐insulin resistance, total cholesterol, triglyceride, creatinine, aspartate aminotransferase and alanine aminotransferase. By stepwise multiple regression analysis, abdominal visceral fat area, blood pressure and total cholesterol levels independently affected chemerin levels. Conclusions Abdominal visceral fat accumulation, blood pressure and lipid profile were significantly associated with serum chemerin levels. Our findings suggest that chemerin may be a mediator that links visceral obesity to cardiovascular risk factors.     

Relationship between visceral fat accumulation and physical fitness in Japanese women

OBJECTIVE: To investigate the link between visceral fat (V) accumulation and physical fitness. DESIGN: Cross-sectional clinical investigation study. SUBJECTS: Twenty-eight overweight Japanese women with abdominal obesity (abdominal obesity) (body mass index, BMI>or=25, visceral fat area>or=100 cm2) aged 38-65 years (BMI 29.5+/-3.3 kg/m2) were enrolled in this study. They were compared with age and sex matched 28 normal weight subjects (BMI<25, visceral fat area<100 cm2) and 28 overweight subjects without abdominal obesity (overweight) (BMI>or=25, visceral fat area<100 cm2). Measurements: Fat distribution was evaluated by visceral fat and subcutaneous fat (S) areas measured by computed tomography (CT) scanning at umbilical level. Anthropometric parameters, aerobic exercise level, muscle strength, flexibility and blood examination were also investigated. RESULTS: Anthropometric and body composition parameters were significantly higher in abdominal obesity subjects than those in normal weight subjects. BMI, waist circumference, waist hip ratio and visceral fat (V) area were also significantly higher than those in overweight subjects. Reduced oxygen uptake at ventilatory threshold (VT), lowering weight bearing index (WBI), and elevation of blood enzymes were noted in abdominal obesity subjects. There were significant relationships between oxygen uptake at VT and visceral fat area, and also between oxygen uptake at VT and WBI. CONCLUSION: Reduced aerobic exercise level and WBI are characteristic and visceral fat may play an important role for the etiology in Japanese women with abdominal obesity.     

腹型肥胖的研究进展

近年来腹型肥胖作为代谢综合征最重要的特征得到了广泛关注."脂质异位沉积"学说提出腹部皮下脂肪与内脏脂肪一样,在促进胰岛素抵抗形成的过程中发挥关键作用,同时也是导致心血管代谢风险的重要因素,而并非仪表现为既往所认为的机体保护作用.提示无论腹部皮下脂肪还是内脏脂肪堆积引起的腰围增加都应当得到足够的重视,也进一步支持将腰围作为代谢综合征工作定义中肥胖的诊断标准.腹型肥胖的治疗基础仍是生活方式干预,而体液因子、胃肠道激素及棕色脂肪研究的开展为腹型肥胖提供了新的治疗方向.     

Caloric restriction, body fat and ageing in experimental models

Caloric restriction in animal models delays many age‐related pathological conditions. Ageing rats have characteristically increased body weight, fat mass and a specific body fat distribution. This report will focus on the potential cause–effect relationship between increased fat mass and accelerated ageing. In humans, increased fat mass (obesity), and in particular increases in abdominal obesity as a result of deposition of visceral fat, are associated with the metabolic syndrome of ageing. This syndrome is associated with hyperinsulinaemia, dyslipidaemia, type 2 diabetes mellitus, atherosclerosis, hypercoagulability and hypertension. Fat tissue, however, plays a major role by secreting multiple metabolically active factors, which are potentially responsible for the development of insulin resistance. This article will review various experimental models (in animals) used to prevent insulin resistance of ageing by decreasing fat mass, and in particular, decreasing visceral fat. We suggest that this decrease in fat mass and its beneficial repercussions observed in ageing animal models may apply also to human ageing and its related pathology.     

The link between abdominal obesity and the metabolic syndrome

The clustering of cardiovascular risk factors associated with abdominal obesity is well established. Although currently lacking a universal definition, the metabolic syndrome describes a constellation of metabolic abnormalities, including abdominal obesity, and was originally introduced to characterize a population at high cardiovascular risk. Adipose tissue is a dynamic endocrine organ that secretes several inflammatory and immune mediators known as adipokines. Dysregulation of adipokine secretion, free fatty acid toxicity, and the site-specific differences in abdominal (visceral) versus subcutaneous fat support abdominal obesity as a causal factor mediating the insulin resistance, increased risk of diabetes, and cardiovascular disease in the metabolic syndrome.     

WILLENDORF AWARDAW0001Establishment of the concept of visceral fat syndrome and the discovery of adiponectin

Clinical studies in recent years have demonstrated that the extent of obesity does not necessarily determine the development of obesity‐related diseases such as type2 diabetes, hyperlipidemia, hypertension, but fat distribution is a much more important determinant In 1983, we reported a method for fat analysis using CT scan which enabled us to analyze in intraabdominal adipose tissue, namely visceral fat as well as subcutaneous fat. Then we demonstrated that visceral fat accumulation correlated to the disturbance of lipid and glucose metabolism, insulin resistance, hypertension and cardiovascular disease in obese subjects and even in non‐obese subjects. From these clinical studies, we proposed the concept of ‘visceral fat syndrome’ in which multiple risk factors cluster through visceral fat accumulation. Besides, this syndrome is designated to be a very atherogenic state. Visceral fat syndrome is corresponding to the concept of metabolic syndrome recently noted. In order to clarify the molecular mechanism why visceral fat accumulation correlates to plural common diseases and also directly to atherosclerosis, we started a project for the analysis of adipose tissue using random sequence of expressed genes in adipose tissues. We found unexpectedly that adipose tissue, especially visceral fat, expressed strongly the genes encoding secretory proteins most of which are important bioactive substances (named as adipocytokines). In addition to known adipocytokines, several novel adipose‐specific genes were identified. Among them, a collagen‐like protein encoded by an adipose most abundant gene (apM‐1) is the most important novel adipocytokine which is named adiponectin. Adiponectin has anti‐diabetic, anti‐atherogenic, anti‐oncogenic and anti‐inflammatory properties and its plasma levels decreases with visceral fat accumulation, suggesting that this molecules may play a central role in the visceral fat syndrome or metabolic syndrome. In this lecture, I would like to present the importance of adiponectin together with other adipocytokines in lifestyle‐related diseases relevant to visceral fat accumulation.     

Effects of physical training on anthropometrics,physical and physiological capacities in individuals with obesity: A systematic review

Increasing the amount of physical activity is an important strategy for weight loss. This systematic review summarizes recent findings on the effects of physical training on anthropometric characteristics, physical performances and physiological capacities in individuals with overweight and obesity. A systematic literature search strategy was conducted from inception until June 2019 using four electronic databases that identified 2,708 records. After screening for titles, abstracts and full texts, 116 studies were included in our final analysis. Both aerobic (e.g., endurance training) and anaerobic training (e.g., high‐intensity training, resistance training) improved body composition and physical fitness indicators in adults, adolescents and children with obesity (effect size: 0.08 < d < 2.67, trivial to very large). This systematic review suggests that both low‐ and high‐intensity training significantly reduced body weight and fat mass while increasing fat‐free mass in individuals with obesity (effect size: 0.04 <d <3.2, trivial to very large). A significant increase in VO_2max also occurs in individuals with obesity in response to aerobic training or high‐intensity interval training (effect size: 0.13 < d < 6.24, trivial to very large). Further studies are needed to define the optimal combination of training intensity and duration needed to produce the most efficacious results in individuals with obesity.     

Cutoff points of abdominal obesity indices in screening for non‐alcoholic fatty liver disease in Asians

Background/aims: Abdominal obesity is associated with metabolic syndrome and non‐alcoholic fatty liver disease (NAFLD). Although there have been many studies to determine the optimal cutoff points of waist circumference or visceral fat area in screening for metabolic syndrome, there have been no reports to establish adequate cutoff points of abdominal obesity indices in screening for NAFLD. Therefore, we examined the appropriate cutoff points of abdominal obesity indices associated with NAFLD in Korean men and women using receiver operating characteristic (ROC) curve analysis. Furthermore, we compared the usefulness of various abdominal obesity indices measured using computed tomography (CT), dual‐energy X‐ray absorptiometry (DXA) and anthropometric parameters for detecting NAFLD. Methods: We analysed the baseline data of an ongoing prospective, observational cohort study, including a total of 456 healthy subjects 20–88 years of age. NAFLD was diagnosed by unenhanced CT using the liver attenuation index. Results: All ROC curves of waist circumference, waist‐to‐height ratio, DXA‐measured trunk fat mass and CT‐measured visceral fat area were significantly above the diagonal line. There were no significant differences in the area under the curve values among these abdominal obesity indices in each gender. The appropriate cutoff point of waist circumference in screening for NAFLD was 89 cm for men and 84 cm for women and the optimal cutoff point of waist‐to‐height ratio was 0.52 for men and 0.53 for women with very high negative predictive values. Conclusions: The simple anthropometric parameters, such as waist circumference and waist‐to‐height ratio, are as useful as DXA and CT for predicting NAFLD in Korean adults.     

Quadriceps sarcopenia and visceral obesity are risk factors for postural instability in the middle‐aged to elderly population

Aim: Aging shifts body composition to comprising more fat and less muscle. Sarcopenia, particularly in the knee extensors, and obesity, particularly visceral obesity, either alone or in combination, may exacerbate age‐related physical disability. We investigated the association between age‐related quadriceps (Qc) sarcopenia and visceral obesity, as measured by cross‐sectional area (CSA), on postural instability. Methods: Mid‐thigh muscle CSA and abdominal visceral and subcutaneous fat area at the level of the umbilicus were assessed from computed tomography (CT) images in 410 apparently healthy independent middle‐aged to elderly subjects attending the medical check‐up program in Ehime University Hospital. Static postural instability using a posturograph and one‐leg standing time with eyes open were assessed. Results: Both abdominal visceral fat area and Qc muscle CSA corrected by body weight (BW) were associated with static postural instability, in addition to age and sex, while BW‐corrected Qc muscle CSA predicted a short one‐leg standing time. The combination of Qc sarcopenia, defined as greater than 1 standard deviation below the mean of a young group (age <60 years), and visceral obesity, defined as a visceral fat area of more than 100 cm², were associated with static postural instability, while Qc sarcopenia was related to a higher prevalence of one‐leg standing time of less than 30 s, irrespective of visceral obesity. Conclusion: Thigh Qc sarcopenia and visceral obesity are associated with postural instability in middle‐aged to elderly subjects. These findings suggest that age‐related, site‐specific fat and muscle mass alterations are associated with functional impairment. Geriatr Gerontol Int 2010; 10: 233–243.     

Abdominal visceral fat reduction is associated with favorable changes of serum retinol binding protein-4 in nondiabetic subjects

The adipocytokine retinol binding protein-4 (RBP4) has recently been shown to link obesity and insulin resistance, although their relationship remains controversial in human studies. The influence of weight reduction with changes of fat distribution on serum RBP4 concentration in nondiabetics is also unknown. We assessed the effect of weight reduction (especially abdominal visceral fat loss) on serum RBP4 levels after a structuralized weight-reduction program. We conducted a prospective intervention study consisting of a 16-week weight reduction program, including lifestyle modification and adjuvant appetite suppressants. A total of 52 nondiabetic subjects aged 37.4 +/- 11 years with a body mass index of 27.4 +/- 4 kg/m (2) were included. Serum RBP4 concentrations with other metabolic parameters and abdominal adipose tissue areas as determined by computed tomography scan were measured both before and 16 weeks after the weight reduction program. Subjects had a 10.9% loss of body weight accompanied by a 25.5% decrease in serum RBP4 levels, with improved ( ) insulin sensitivity after the program. The changes in RBP4 levels were significantly correlated with the amounts of abdominal visceral fat loss (r = 0.38, p<0.01) but were not associated with the amount of total body fat loss or abdominal subcutaneous fat loss. Weight reduction, especially the loss of abdominal visceral fat, lowers serum RBP4 concentrations in nondiabetic subjects. The relationship between individual changes in RBP4 and abdominal visceral fat indicated that RBP4 may be involved in the beneficial effect of visceral fat reduction on the improvement of insulin resistance and metabolic syndrome.     

Influence of metabolic syndrome on upper gastrointestinal disease

A recent increase in the rate of obesity as a result of insufficient physical exercise and excess food consumption has been seen in both developed and developing countries throughout the world. Additionally, the recent increased number of obese individuals with lifestyle-related diseases associated with abnormalities in glucose metabolism, dyslipidemia, and hypertension, defined as metabolic syndrome (MS), has been problematic. Although MS has been highlighted as a risk factor for ischemic heart disease and arteriosclerotic diseases, it was also recently shown to be associated with digestive system disorders, including upper gastrointestinal diseases. Unlike high body weight and high body mass index, abdominal obesity with visceral fat accumulation is implicated in the onset of various digestive system diseases because excessive visceral fat accumulation may cause an increase in intra-abdominal pressure, inducing the release of various bioactive substances, known as adipocytokines, including tumor necrosis factor-α, interleukin-6, resistin, leptin, and adiponectin. This review article focuses on upper gastrointestinal disorders and their association with MS, including obesity, visceral fat accumulation, and the major upper gastrointestinal diseases.     

Muscle tissue in obesity with different distribution of adipose tissue. Effects of physical training

Obese men and women with the same body fat mass, as well as obese women in another study, were divided into groups with male or female type of body fat distribution, but again with similar body fat mass. The participants were examined with measurements of body composition, including muscle fiber distribution, as well as circulatory and metabolic variables before and after physical training under controlled conditions. Obese men had higher lean body mass, blood pressure, blood glucose and plasma insulin, C-peptide, cholesterol and triglyceride concentrations than age- and body fat-matched obese women. Obese women with male type of adipose tissue distribution showed the same differences (except cholesterol) in comparisons with women with female type of adipose tissue distribution. The women with male type obesity were also more insulin resistant in glucose clamp measurements, and had male type of muscle fiber distribution. Physical training in the group of obese men resulted in a decrease of body fat, a further increase of lean body mass, an increase of fast twitch, aerobic type, muscle fibres as well as lower plasma insulin, cholesterol and triglyceride concentrations and lower blood pressure. Obese women with male type distribution of adipose tissue responded to physical training essentially like men. The insulin sensitivity was improved to the same level as in obese women with female type of adipose tissue distribution. In contrast, the latter women showed an increase of body fat and no metabolic improvements after training. These results show that obese women with male type of body fat distribution also have male characteristics of muscle mass, morphology and function. It is suggested that the obesity complications associated with this condition are improved by physical training because of an adaptation to a negative energy balance, in combination with an improvement of insulin sensitivity of the muscle mass. In contrast, the failure of obese women with female type of adipose tissue distribution to adapt to a negative energy balance during physical training is probably explaining their failure to decrease body fat and to improve metabolism during physical training.     

Metabolic obesity: the paradox between visceral and subcutaneous fat

In contrast to the accumulation of fat in the gluteo-femoral region, the accumulation of fat around abdominal viscera and inside intraabdominal solid organs is strongly associated with obesity-related complications like Type 2 diabetes and coronary artery disease. The association between visceral adiposity and accelerated atherosclerosis was shown to be independent of age, overall obesity or the amount of subcutaneous fat. Recent evidence revealed several biological and genetic differences between intraabdominal visceral-fat and peripheral subcutaneous-fat. Such differences are also reflected in their contrasting roles in the pathogenesis of obesity-related cardiometabolic problems, in either lean or obese individuals. The functional differences between visceral and the subcutaneous adipocytes may be related to their anatomical location. Visceral adipose tissue and its adipose-tissue resident macrophages produce more proinflamatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and less adiponectin. These cytokines changes induce insulin resistance and play a major role in the pathogenesis of endothelial dysfunction and subsequent atherosclerosis. The rate of visceral fat accumulation is also different according to the individual's gender and ethnic background; being more prominent in white men, African American women and Asian Indian and Japanese men and women. Such differences may explain the variation in the cardiometabolic risk at different waist measurements between different populations. However, it is unclear how much visceral fat reduction is needed to induce favorable metabolic changes. On the other hand, peripheral fat mass is negatively correlated with atherogenic metabolic risk factors and its selective reduction by liposuction does improve cardiovascular risk profile. The increasing knowledge about body fat distribution and its modifiers may lead to the development of more effective treatment strategies for people with/or at high risk for Type 2 diabetes and coronary artery disease. These accumulating observations also urge our need for a new definition of obesity based on the anatomical location of fat rather than on its volume, especially when cardiometabolic risk is considered. The term "Metabolic Obesity", in reference to visceral fat accumulation in either lean or obese individuals may identify those at risk for cardiovascular disease better than the currently used definitions of obesity.     

The effects of weight loss treatments on upper and lower body fat

The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may have comparable amounts of adipose tissue but remain relatively free from the metabolic consequences of obesity. This raises an obvious question-are there particular weight reducing treatments which specifically target intra-abdominal fat? In theory, surgical removal of upper body fat should be effective. In reality, neither liposuction nor apronectomy ('tummy tuck') have any beneficial metabolic effects, they simply remove subcutaneous adipose tissue which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass operations may be dramatically effective in improving blood pressure, insulin sensitivity and glucose tolerance. However, these benefits result from a parallel reduction in visceral and total body fat. Studies of body fat distribution in postmenopausal women confirm that the marked decrease in adiposity, following a programme of very low calorie diet and exercise, reflects a comparable reduction in visceral and thigh fat. The reduction in waist circumference after a low fat/exercise programme suggests a similar situation in men. Exercise has an important role in treatment but, once again, the fat loss is generalised. Nevertheless, the improved metabolic parameters seen in exercising obese subjects, independent of weight loss, suggest other beneficial actions. Growth hormone (GH) has a marked lipolytic action. GH replacement treatment for GH deficient adults with pronounced abdominal fat deposition, has been shown to reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal subcutaneous fat. Similar beneficial actions on abdominal fat have been reported following treatment with testosterone in obese men. The potential hazards of such treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective in reducing total body fat but the results from a six month randomised controlled trial indicates that it does not specifically influence changes in waist circumference associated with weight loss. In conclusion, any treatment which reduces total body fat will, by its nature, reduce intra-abdominal visceral fat. There are presently no specific treatments which can be recommended for intra-abdominal fat but increasing knowledge of the biochemical aberrations associated with visceral adiposity may lead to more specific therapies for the future.     

The new adipose tissue and adipocytokines

Obesity is a well-known risk factor for the development of insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. Rather than the total amount of fat, central distribution of adipose tissue is very important in the pathophysiology of this constellation of abnormalities termed metabolic syndrome. Adipose tissue, regarded only as an energy storage organ until the last decade, is now known as the biggest endocrine organ of the human body. This tissue secretes a number of substances--adipocytokines--with multiple functions in metabolic profile and immunological process. Therefore, excessive fat mass may trigger metabolic and hemostatic disturbances as well as CVD. Adipocytokines may act locally or distally as inflammatory, immune or hormonal signalers. In this review we discuss visceral obesity, the potential mechanisms by which it would be related to insulin resistance, methods for its assessment and focus on the main adipocytokines expressed and secreted by the adipose tissue. Particularly, we review the role of adiponectin, leptin, resistin, angiotensinogen, TNF-alpha, and PAI-1, describing their impact on insulin resistance and cardiovascular risk, based on more recent findings in this area.     

Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = -0.22), or physical activity energy expenditure (r = -0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 +/- 0.14 vs. 0.66 +/- 0.28 mmol/kg x min; P < 0.05). Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.