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.     

Relationship between abdominal visceral fat and lacunar infarcts in Japanese men.

BACKGROUND: The relationship between abdominal visceral fat accumulation and lacunar infarcts has not been previously investigated in Japanese men. METHODS AND RESULTS: The subjects were 637 middle-aged (40-64 years) and 222 elderly (65-79 years) men who participated in a health checkup program from 1999 to 2003. The association between lacunar infarcts identified by magnetic resonance imaging and cardiovascular risk factors, including abdominal visceral fat accumulation evaluated by computed tomography, was examined. The prevalence of lacunar infarcts was 4.9%. Hypertension was associated with lacunar infarcts among both the middle-aged men [age-adjusted odds ratio (OR)=2.9 (95% confidence interval (CI): 1.1-7.8)] and the elderly men [OR=5.1 (95%CI: 1.4-19.0)]. Abdominal visceral fat accumulation was slightly associated with lacunar infarcts among middle-aged men, but not among elderly men: OR in the highest (>or=117 cm(2)) vs lowest (or=143 cm(2)) was still slightly associated with lacunar infarcts after adjustment for age, hypertension, drinking and smoking among middle-aged men [OR=2.7 (95%CI: 0.8-9.1)]. CONCLUSIONS: This cross-sectional study suggests that abdominal visceral fat accumulation is a possible risk factor of lacunar infarcts, in addition to hypertension, in middle-aged Japanese men.     

Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy

Objective Androgen deprivation therapy (ADT) for prostate cancer is associated with increases in fat mass and risk of type 2 diabetes; however, the relationship between sex steroid deficiency and abdominal fat distribution remains controversial. Design We conducted a 12‐month prospective observational study at a tertiary referral centre. Patients and measurements We investigated changes in abdominal fat distribution and insulin resistance in 26 men (70·6 ± 6·8 years) with nonmetastatic prostate cancer during the first year of ADT. Results Twelve months of ADT increased visceral abdominal fat area by 22% (from 160·8 ± 61·7 to 195·9 ± 69·7 cm²; P < 0·01) and subcutaneous abdominal fat area by 13% (from 240·7 ± 107·5 to 271·3 ± 92·8 cm²; P < 0·01). Fat mass increased by 14% (+3·4 kg; P < 0·001) and lean tissue mass decreased by 3·6% (?1·9 kg; P < 0·001). Insulin resistance (HOMA‐IR) increased by 12% (2·50 ± 1·12 to 2·79 ± 1·31, P < 0·05). There was no change in fasting glucose or glycated haemoglobin levels. Total testosterone (TT) was inversely associated with visceral fat area independent of oestradiol (E2), but E2 was not associated with visceral fat area independent of TT. Visceral fat area, not TT or E2, was independently associated with insulin resistance. Conclusions ADT for prostate cancer results in accumulation of both visceral and subcutaneous abdominal fat. Increased visceral fat area appears more closely linked to testosterone than oestradiol deficiency. Increased insulin resistance may arise secondary to visceral fat accumulation, rather than as a direct result of sex steroid deficiency.     

Relationship between absorptiometry and ultrasound measurements of abdominal subcutaneous fat tissue in postmenopausal women

The purpose of this study was to describe the association of abdominal subcutaneous adipose tissue (SAT) as assessed by ultrasound with fat tissue in the abdomen, trunk, and other areas as measured by DXA in 101 postmenopausal Caucasian women (62.5 years; 27.3 kg/m(2); 43.0% body fat). Ultrasound SAT thickness was calculated with electronic calipers positioned at the skin-fat and fat-muscle computer screen interface, at the suprailiac (SUPT) and abdominal (ABDT) sites. Pearson correlation showed significant ( p<0.001) coefficients between SAT by DXA at both ABDT ( r=0.644) and SUPT ( r=0.537). Other DXA measurements were also associated ( p<0.001) with SAT assessed by DXA and ultrasound. In postmenopausal women, DXA estimates of subcutaneous and total adiposity are moderately associated with ultrasound measures of fat in the abdomen. Future research at our and other laboratories should clarify the clinical and practical significance of these findings.     

Cardiovascular-related proteins and the abdominal visceral to subcutaneous adipose tissue ratio

Background and aimsAn increased amount of visceral adipose tissues has been related to atherosclerosis and future cardiovascular events. The present study aims to investigate how the abdominal fat distribution links to plasma levels of cardiovascular-related proteins.Method and resultsIn the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 326, all aged 50 years), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue volumes were quantified by MRI. Eighty-six cardiovascular-related proteins were measured by the proximity extension assay (PEA). Similar investigations were carried out in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 400, all aged 75 years).In the discovery dataset (POEM), 10 proteins were related to the VAT/SAT-ratio using false discovery rate <.05. Of those, Cathepsin D (CTSD), Interleukin-1 receptor antagonist protein (IL-1RA) and Growth hormone (GH) (inversely) were related to the VAT/SAT-ratio in the validation in PIVUS following adjustment for sex, BMI, smoking, education level and exercise habits (p < 0.05). In a secondary analysis, a meta-analysis of the two samples suggested that 15 proteins could be linked to the VAT/SAT-ratio following adjustment as above and Bonferroni-correction of the p-value.ConclusionThree cardiovascular-related proteins, cathepsin D, IL-1RA and growth hormone, were being associated with the distribution of abdominal adipose tissue using a discovery/validation approach. A meta-analysis of the two samples suggested that also a number of other cardiovascular-related proteins could be associated with an unfavorable abdominal fat distribution.     

The role of insulin resistance in the relation of visceral,abdominal subcutaneous and total body fat to cardiovascular function

Background and aimsThe separate cardiovascular effects of type 2 diabetes and adiposity remain to be examined. This study aimed to investigate the role of insulin resistance in the relations of visceral (VAT), abdominal subcutaneous (aSAT) adipose tissue and total body fat (TBF) to cardiovascular remodeling.Methods and resultsIn this cross-sectional analysis of the population-based Netherlands Epidemiology of Obesity study, 914 middle-aged individuals (46% men) were included. Participants underwent magnetic resonance imaging. Standardized linear regression coefficients (95%CI) were calculated, adjusted for potential confounding factors. All fat depots and insulin resistance (HOMA-IR), separate from VAT and TBF, were associated with lower mitral early and late peak filling rate ratios (E/A): −0.04 (−0.09;0.01) per SD (54 cm²) VAT; −0.05 (−0.10;0.00) per SD (94 cm²) aSAT; −0.09 (−0.16;-0.02) per SD (8%) TBF; −0.11 (−0.17;-0.05) per 10-fold increase in HOMA-IR, whereas VAT and TBF were differently associated with left ventricular (LV) end-diastolic volume: −8.9 (−11.7;-6.1) mL per SD VAT; +5.4 (1.1;9.7) mL per SD TBF. After adding HOMA-IR to the model to evaluate the mediating role of insulin resistance, change in E/A was −0.02 (−0.07;0.04) per SD VAT; −0.03 (−0.08;0.02) per SD aSAT; −0.06 (−0.13;0.01) per SD TBF, and change in LV end-diastolic volume was −7.0 (−9.7;-4.3) mL per SD VAT. In women, adiposity but not HOMA-IR was related to higher aortic arch pulse wave velocity.ConclusionInsulin resistance was associated with reduced diastolic function, separately from VAT and TBF, and partly mediated the associations between adiposity depots and lower diastolic function.     

Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men

Aging is associated with reduced GH, IGF-I, and sex steroid axis activity and with increased abdominal fat. We employed a randomized, double-masked, placebo-controlled, noncross-over design to study the effects of 6 months of administration of GH alone (20 microg/kg BW), sex hormone alone (hormone replacement therapy in women, testosterone enanthate in men), or GH + sex hormone on total abdominal area, abdominal sc fat, and visceral fat in 110 healthy women (n = 46) and men (n = 64), 65-88 yr old (mean, 72 yr). GH administration increased IGF-I levels in women (P = 0.05) and men (P = 0.0001), with the increment in IGF-I levels being higher in men (P = 0.05). Sex steroid administration increased levels of estrogen and testosterone in women and men, respectively (P = 0.05). In women, neither GH, hormone replacement therapy, nor GH + hormone replacement therapy altered total abdominal area, sc fat, or visceral fat significantly. In contrast, in men, administration of GH and GH + testosterone enanthate decreased total abdominal area by 3.9% and 3.8%, respectively, within group and vs. placebo (P = 0.05). Within-group comparisons revealed that sc fat decreased by 10% (P = 0.01) after GH, and by 14% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, sc fat decreased by 14% (P = 0.05) after GH, by 7% (P = 0.05) after testosterone enanthate, and by 16% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, visceral fat did not decrease significantly after administration of GH, testosterone enanthate, or GH + testosterone enanthate. These data suggest that in healthy older individuals, GH and/or sex hormone administration elicits a sexually dimorphic response on sc abdominal fat. The generally proportionate reductions we observed in sc and visceral fat, after 6 months of GH administration in healthy aged men, contrast with the disproportionate reduction of visceral fat reported after a similar period of GH treatment of nonelderly GH deficient men and women. Whether longer term administration of GH or testosterone enanthate, alone or in combination, will reduce abdominal fat distribution-related cardiovascular risk in healthy older men remains to be elucidated.     

Metabolic effects of visceral fat accumulation in type 2 diabetes

Visceral fat (VF) excess has been associated with decreased peripheral insulin sensitivity and has been suggested to contribute to hepatic insulin resistance. However, the mechanisms by which VF impacts on hepatic glucose metabolism and the quantitative role of VF in glycemic control have not been investigated. In the present study 63 type 2 diabetic subjects (age, 55 +/- 1 yr; fasting plasma glucose, 5.5-14.4 mmol/liter; hemoglobin A(1c), 6.1-11.7%) underwent measurement of 1) fat-free mass ((3)H(2)O technique), 2) sc and visceral abdominal fat area (magnetic resonance imaging), 3) insulin sensitivity (euglycemic insulin clamp), 4) endogenous glucose output ([(3)H]glucose infusion technique), and 5) gluconeogenesis ((2)H(2)O method). After adjustment for sex, age, body mass index, diabetes duration, ethnicity, and sc fat area, VF area was positively related to fasting hyperglycemia (partial r = 0.46; P = 0.001) as well as to hemoglobin A(1c) (partial r = 0.50; P = 0.0003). Insulin sensitivity was reciprocally related to VF independently of body mass index (partial r = 0.33; P = 0.01). In contrast, the relation of basal endogenous glucose output to VF was not statistically significant. This lack of association was explained by the fact that VF was positively associated with gluconeogenesis flux (confounder-adjusted, partial r = 0.45; P = 0.003), but was reciprocally associated with glycogenolysis (partial r = 0.31; P < 0.05). We conclude that in patients with established type 2 diabetes, VF accumulation has a significant negative impact on glycemic control through a decrease in peripheral insulin sensitivity and an enhancement of gluconeogenesis.     

PPARgamma activity in subcutaneous abdominal fat tissue and fat mass gain during short-term overfeeding

OBJECTIVE: As the peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in fat mass regulation, we investigated whether initial subcutaneous PPARgamma activity is related to fat mass generation during overfeeding. SUBJECTS: Fourteen healthy female subjects (age 25 +/- 4 years, BMI 22.1 +/- 2.3 kg/m2). DESIGN AND MEASUREMENTS: Subjects were overfed with a diet supplying 50% more energy than baseline energy requirements for 14 days. Fasting blood samples were analyzed for leptin, insulin and glucose. Fasting subcutaneous abdominal fat biopsies were obtained for analysis of PPARgamma1, PPARgamma2, aP2 and UCP2 mRNAs. RESULTS: Initial PPARgamma1 and 2, aP2 and UCP2 mRNAs were not related to fat gain (P > 0.12). However, PPARgamma1, PPARgamma2 and aP2 mRNA changes were positively related to changes in plasma leptin (P < 0.05) and, except aP2 (P = 0.06), to fat gain (P < 0.05). PPARgamma and aP2 mRNA changes were positively related (P<0.01), indicating that PPARgamma mRNA levels reflected PPARgamma activity. CONCLUSION: These data suggest that the ability to increase PPARgamma activity might be involved in the susceptibility to gain weight during a positive energy balance.     

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.     

Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity

Obesity is related to the risk for developing non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and cardiovascular disease. Visceral adipose tissue (VAT) has been proposed to mediate these relationships. Abdominal subcutaneous adipose tissue (SAT) is divided into 2 layers by a fascia, the fascia superficialis. Little is known about the radiologic anatomy or metabolic correlates of these depots. The objective of this study was to relate the amounts of VAT, SAT, deep subcutaneous abdominal adipose tissue (DSAT), and superficial subcutaneous abdominal adipose tissue (SSAT) to gender and the metabolic complications of obesity after adjusting for total body fat and to discuss the implications of these findings on the measurement of adipose tissue mass and adipose tissue function. The design was a cross-sectional database study set in a nutrition research center. Subjects included 199 volunteers participating in nutrition research protocols who also had computed tomography (CT) and dual energy x-ray absorptiometry (DEXA) measurement of body fat. The amount of DSAT was sexually dimorphic, with women having 51% of the subcutaneous abdominal fat in the deep layer versus 66% for men (P <.05). Abdominal fat compartments were compared with metabolic variables before and after adjusting for body fat measured by DEXA using 2 separate methods. The unadjusted correlation coefficients between the body fat measures, R(2), were largest for fasting insulin and triglyceride and smaller for high-density lipoprotein (HDL) cholesterol and blood pressure. A large portion of the variance of fasting insulin levels in both men and women was explained by total body fat. In both men and women, the addition of VAT and subcutaneous abdominal adipose tissue depots only slightly increased the R(2). In men, when body fat compartments were considered independently, DSAT explained a greater portion of the variance (R(2) =.528) in fasting insulin than VAT (R(2) =.374) or non-VAT, non-DSAT subcutaneous adipose tissue (R(2) =.375). These data suggest that total body fat is a major contributor to the metabolic sequelae of obesity, with specific fat depots, VAT, and DSAT also making significant contributions.     

Ethnic differences in abdominal visceral fat accumulation between Japanese, African-Americans, and Caucasians: a meta-analysis

A meta-analysis was performed in order to test the hypothesis that Japanese have a greater amount of abdominal visceral fat (AVF) relative to abdominal subcutaneous fat (ASF) than Caucasians. Data were derived from published studies that included mean values for AVF and ASF areas, measured using computed tomography, and age for native Japanese, African-Americans, and Caucasians of both genders. Mean values from each study were used as single data points. A significant difference in AVF was observed between Japanese and Caucasian populations after adjusting for ASF, age, and sex ( p<0.05). However, the difference in AVF between Japanese and Caucasian females was lower than that between African-American and Caucasian females.