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.     

Circulating IL-6 concentrations and abdominal adipocyte isoproterenol-stimulated lipolysis in women

Objective: To examine the association of plasma interleukin‐6 (IL‐6) concentrations with adiposity and fat cell metabolism in women. Methods and Procedures: Omental (OM) and subcutaneous (SC) adipose tissue samples were obtained from 48 healthy women (age: 47 ± 5 years, BMI: 26.9 ± 5.3 kg/m²) undergoing gynecological surgeries. Total and visceral adiposity were assessed by dual‐energy X‐ray absorptiometry and computed tomography, respectively. Measures of adipocyte lipolysis (basal, isoproterenol‐, forskolin‐, and cyclic dibutyryl‐adenosine monophosphate (AMP)‐stimulated) and adipose tissue lipoprotein lipase (LPL) activity were obtained. Plasma IL‐6 was measured by radioimmunoassay. Results: Plasma IL‐6 was positively correlated with total body fat mass (r = 0.32, P < 0.05), SC adipose tissue area (r = 0.35, P < 0.05), SC adipocyte diameter (r = 0.30, P < 0.05), and a trend was observed with visceral adipose tissue area (r = 0.20, P < 0.07). Plasma IL‐6 was positively correlated with glycerol released in response to isoproterenol (10^?5 to 10^?8 mol/l) by isolated SC (0.31 ≤ r ≤ 0.65, P < 0.05) and OM (0.36 ≤ r ≤ 0.40, P < 0.02) adipocytes, independent of menopausal status. No correlation was found with LPL activity. A subsample of women with high plasma IL‐6 (n = 10) was matched with women with low plasma IL‐6 (n = 10) for total body fat mass. OM adipocyte glycerol release in response to isoproterenol (10^?5 to 10^?8 mol/l) was higher in the subsample of women with elevated plasma IL‐6 (P ≤ 0.07). Discussion: We observed that OM lipolysis was significantly higher in women with elevated plasma IL‐6 for a similar body fat mass and menopausal status. These results suggest that higher circulating IL‐6 concentrations are associated with increased isoproterenol‐stimulated lipolysis especially in OM abdominal adipocytes in women.     

Postabsorptive VLDL‐TG Fatty Acid Storage in Adipose Tissue in Lean and Obese Women

Adipose tissue lipoprotein lipase (LPL) is a necessary enzyme for storage of very‐low‐density lipoprotein–triglyceride (VLDL‐TG), but whether it is a rate‐determining step is unknown. To test this hypothesis we included 10 upper‐body obese (UBO), 11 lower‐body obese (LBO), and 8 lean women. We infused ex vivo‐labeled VLDL‐¹⁴C‐TG and then performed adipose tissue biopsies to understand the relationship between VLDL‐TG storage and LPL activity in femoral and upper‐body subcutaneous fat. Both fractional tracer storage and rate of storage of the VLDL‐TG tracer were evaluated. VLDL‐TG storage was also examined as a function of regional adipose tissue blood flow (ATBF), insulin, VLDL‐TG turnover, regional fat mass, fat‐free mass (FFM), and fat cell size. LPL activity per adipocyte was significantly greater in obese than lean women but not significantly different per gram lipid. Both VLDL‐TG fractional tracer storage per kg lipid and VLDL‐TG storage rate per kg lipid were similar in abdominal and femoral fat in all three groups and were not significantly different between groups. Multiple regression analysis identified FFM and femoral fat mass as significant independent predictors of VLDL‐TG fractional tracer storage and insulin as a significant predictor of VLDL‐TG fatty acid storage rate. LPL activity, ATBF, and VLDL‐TG turnover did not predict VLDL‐TG storage. We conclude that lower FFM and greater plasma insulin are associated with greater VLDL‐TG deposition in abdominal subcutaneous and femoral fat. Greater femoral fat mass signals greater femoral VLDL‐TG storage. We suggest that the differences in VLDL‐TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL activity.     

Body Fat Distribution and Inflammation Among Obese Older Adults With and Without Metabolic Syndrome

The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI ≥30 kg/m²), aged 70–79 participating in the Health, Aging and Body Composition (Health ABC) study. Thirty‐one percent of these obese men and women did not have metabolic syndrome. Obese persons with metabolic syndrome had significantly more abdominal visceral fat (men: P = 0.04; women: P < 0.01) and less thigh subcutaneous fat (men: P = 0.09; women: P < 0.01) than those without metabolic syndrome. Additionally, those with metabolic syndrome had significantly higher levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and plasminogen activator inhibitor‐1 (PAI‐1) than individuals without metabolic syndrome. Per standard deviation higher in visceral fat, the likelihood of metabolic syndrome significantly increased in women (odds ratio (OR): 2.16, 95% confidence interval (CI): 1.59–2.94). In contrast, the likelihood of metabolic syndrome decreased in both men (OR: 0.56, 95% CI: 0.39–0.80) and women (OR: 0.49, 95% CI: 0.34–0.69) with each standard deviation higher in thigh subcutaneous fat. These associations were partly mediated by adipocytokines; the association between thigh subcutaneous fat and metabolic syndrome was no longer significant in men. In summary, metabolically healthy obese older persons had a more favorable fat distribution, characterized by lower visceral fat and greater thigh subcutaneous fat and a more favorable inflammatory profile compared to their metabolically unhealthy obese counterparts.     

The stromal‐vascular fraction of adipose tissue contributes to major differences between subcutaneous and visceral fat depots

Adipose tissue represents a complex tissue both in terms of its cellular composition, as it includes mature adipocytes and the various cell types comprising the stromal‐vascular fraction (SVF), and in relation to the distinct biochemical, morphological and functional characteristics according to its anatomical location. Herein, we have characterized the proteomic profile of both mature adipocyte and SVF from human visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) fat depots in order to unveil differences in the expression of proteins which may underlie the distinct association of VAT and SAT to several pathologies. Specifically, 24 proteins were observed to be differentially expressed between SAT SVF versus VAT SVF from lean individuals. Immunoblotting and RT‐PCR analysis confirmed the differential regulation of the nuclear envelope proteins lamin A/C, the membrane‐cytoskeletal linker ezrin and the enzyme involved in retinoic acid production, aldehyde dehydrogenase 1A2, in the two fat depots. In sum, the observation that proteins with important cell functions are differentially distributed between VAT and SAT and their characterization as components of SVF or mature adipocytes pave the way for future research on the molecular basis underlying diverse adipose tissue‐related pathologies such as metabolic syndrome or lipodystrophy.     

Ethnic‐Specific Differences in Abdominal Subcutaneous Adipose Tissue Compartments

South Asians have a higher prevalence of cardiovascular disease (CVD) than Europeans. Studies have identified distinct subcompartments of subcutaneous adipose tissue (SAT) that provide insight into the relationship between abdominal obesity and metabolic risk factors in different ethnic groups. Our objective was to determine the relationship between SAT compartments and fat‐free mass (FFM) between South Asian and European cohorts, and between men and women. Healthy Europeans and South Asians (n = 408) were assessed for FFM via dual energy X‐ray absorptiometry, and SAT areas by computed tomography (CT). SAT was subdivided into superficial subcutaneous abdominal adipose tissue (SSAT) and deep subcutaneous abdominal adipose tissue (DSAT). Linear regression analyses were performed using DSAT and SSAT as separate dependent variables and FFM and ethnicity as primary independent variables adjusting for age, gender, income, education, and smoking status. Results showed that South Asian men had significantly higher amounts of DSAT (median 187.65 cm² vs. 145.15 cm², P < 0.001), SSAT (median 92.0 cm² vs. 76.1 cm², P = 0.046), and body fat mass (BFM) (25.1 kg vs. 22.6 kg, P = 0.049) than European men. In a fully adjusted model, South Asians showed significantly greater DSAT at any FFM than Europeans. Women had more SSAT at any given FFM than men and less DSAT at any given FFM than men, irrespective of ethnic background. In conclusion, South Asians had more DSAT than Europeans and men had relatively more DSAT than women. These data suggest that specific fat depots are influenced by ethnicity and gender; therefore, could provide insight into the relationship between ethnicity, gender and subsequent risk for CVD.     

Adipocytes IGFBP‐2 Expression in Prepubertal Obese Children

Aims of the study were to measure insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP‐2 expression, circulating IGFBP‐2, obesity, and insulin sensitivity in obese children. Thirty‐eight obese children were recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test and body composition by total‐body dual‐energy X‐ray absorptiometry. Serum free and total IGF‐I, IGFBP‐2, adiponectin, and leptin were measured. Relative quantification of IGFBP‐2 mRNA by subcutaneous adipose tissue biopsies was obtained using real‐time PCR. Circulating IGFBP‐2 was positively associated with insulin sensitivity, in agreement with previous studies. IGFBP‐2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = ?0.604; P < 0.05), free IGF‐I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP‐2 (r = 0.003, P = ns). The association between IGFBP‐2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate). In conclusion, circulating IGFBP‐2 was positively associated with insulin sensitivity. IGFBP‐2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity. IGFBP‐2 expression may potentially be one of the local mechanisms used by adipocytes to limit further fat gain.     

The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss

Age‐related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ‐agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m²) and women (n = 40, BMI = 33.3 ± 4.9 kg/m²) during weight loss. All participants underwent a 16‐week hypocaloric weight‐loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow‐up using computed tomography (CT). Lean mass was measured using dual X‐ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (?1,160 vs. ?647 cm³, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (?104 vs. ?298 cm³, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: ?43 vs. ?88 cm³, P = 0.005; women: ?34 vs. ?59 cm³, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.     

CD36 is important for adipocyte recruitment and affects lipolysis

Objective: The scavenger receptor CD36 facilitates the cellular uptake of long‐chain fatty acids. As CD36‐deficiency attenuates the development of high fat diet (HFD)‐induced obesity, the role of CD36‐deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design and Methods: Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36^?/? and WT mice after 6 weeks on HFD. Basal lipolysis and insulin‐inhibited lipolysis were investigated in gonadal adipose tissue. Results: CD36^?/? mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes because of a lower number of very small adipocytes (diameter <50 μm). This was accompanied by an increased pool of preadipocytes, which suggests that CD36‐deficiency reduces the capacity of preadipocytes to become adipocytes. Regarding lipolysis, in adipose tissue from CD36^?/? mice, cAMP levels were increased and both basal and 8‐bromo‐cAMP stimulated lipolysis were higher. However, insulin‐mediated inhibition of lipolysis was more potent in CD36^?/? mice. Conclusions: These results indicate that during fat depot expansion, CD36‐deficiency negatively affects preadipocyte recruitment and that in mature adipocytes, CD36‐deficiency is associated with increased basal lipolysis and insulin responsiveness.     

Adiponectin and leptin in African Americans

Objective: African Americans (AAs) have less visceral and more subcutaneous fat than whites, thus the relationship of adiponectin and leptin to body fat and insulin sensitivity in AA may be different from that in whites. Methods and Procedures: Sixty‐nine non‐diabetic AA (37 men and 32 women), aged 33 ± 1 year participated. The percent fat was determined by dual‐energy X‐ray absorptiometry, abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume by computerized tomography (CT), and insulin sensitivity by homeostasis model assessment (HOMA). Results: VAT was greater in men (1,619 ± 177 cm³ vs. 1,022 ± 149 cm³; P = 0.01); women had a higher percentage of body fat (34.1 ± 1.4 vs. 24.0 ± 1.2; P < 0.0001), adiponectin (15.8 ± 1.2 μg/ml vs. 10.4 ± 0.8 μg/ml; P = 0.0004) and leptin (23.2 ± 15.8 ng/ml vs. 9.2 ± 7.2 ng/ml; P < 0.0001). SAT and HOMA did not differ because of the sex. Adiponectin negatively correlated with VAT (r = ?0.41, P < 0.05) in men, and with VAT (r = ?0.55, P < 0.01), and SAT (r = ?0.35, P < 0.05) in women. Adiponectin negatively correlated with HOMA in men (r = ?0.38, P < 0.05) and women (r = ?0.44, P < 0.05). In multiple regression, sex (P = 0.02), HOMA (P = 0.03) and VAT (P = 0.003) were significant predictors of adiponectin (adj R ² = 0.38, P < 0.0001). Leptin positively correlated with VAT, SAT, percent fat and HOMA in men (r = 0.79, r = 0.86, r = 0.89, and r = 0.53; P < 0.001) and women (r = 0.62, r = 0.75, r = 0.83, and r = 0.55; P < 0.01). In multiple regression VAT (P = 0.04), percent body fat (P < 0.0001) and sex (P = 0.01), but not HOMA were significant predictors of serum leptin (adj R ²= 0.82, P < 0.0001). Discussion: The relationship of adiponectin and leptin to body fat content and distribution in AA is dependent on sex. Although VAT and insulin sensitivity are significant determinants of adiponectin, VAT and percent body fat determine leptin.     

Resistin Gene Expression in Human Adipocytes Is Not Related to Insulin Resistance

Objectives: Obesity is an important risk factor for the development of insulin resistance and type 2 diabetes. Recently, a newly described circulating hormone resistin, which is expressed primarily in adipocytes, has been shown to antagonize insulin action in mice. Resistin, therefore, has been suggested to play a role in the pathogenesis of insulin resistance. Research Methods and Procedures: We studied the expression of the resistin gene in primary cultured human adipocytes and preadipocytes. We also examined resistin gene expression in subcutaneous abdominal adipocytes in women (n = 24) over a wide range of body weight and insulin sensitivity. Results: Whereas resistin gene expression was barely detectable in mature adipocytes, it was highly expressed in preadipocytes. Adipogenic differentiation of preadipocytes was associated with a time-dependent down-regulation of resistin gene expression. There was no relationship between body weight, insulin sensitivity, or other metabolic parameters and adipocyte resistin gene expression in the clinical study. Discussion: Together these findings do not support an important role of adipose-tissue resistin gene expression in human insulin resistance.     

Association Between the 4 bp Proinsulin Gene Insertion Polymorphism (IVS‐69) and Body Composition in Black South African Women

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS‐69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS‐69 genotype were measured in 115 normal‐weight (BMI <25 kg/m²) and 138 obese (BMI ≥30 kg/m²) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI ≥35kg/m²) compared with the normal‐weight group (P = 0.029). Obese subjects with the insertion allele had greater fat mass (42.3 ± 0.9 vs. 38.9 ± 0.9 kg, P = 0.034) and fat‐free soft tissue mass (47.4 ± 0.6 vs. 45.1 ± 0.6 kg, P = 0.014), and more abdominal subcutaneous adipose tissue (SAT, 595 ± 17 vs. 531 ± 17 cm², P = 0.025) but not visceral fat (P = 0.739), than obese homozygotes for the wild‐type allele. Only SAT was greater in normal‐weight subjects with the insertion allele (P = 0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild‐type allele in the normal‐weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat‐free soft tissue mass and fat mass, particularly SAT, in obese black South African women.     

Mice Deficient in Phosphofructokinase‐M Have Greatly Decreased Fat Stores

Synthesis of triacylglycerol requires the glucose‐derived glycerol component, and glucose uptake has been viewed as the rate‐limiting step in glucose metabolism in adipocytes. Furthermore, adipose tissue contains all three isoforms of the glycolytic enzyme phosphofructokinase (PFK). We here report that mice deficient in the muscle isoform PFK‐M have greatly reduced fat stores. Mice with disrupted activity of the PFK‐M distal promoter were obtained from Lexicon Pharmaceuticals, developed from OmniBank OST#56064. Intra‐abdominal fat was measured by magnetic resonance imaging of the methylene proton signal. Lipogenesis from labeled glucose was measured in isolated adipocytes. Lipolysis (glycerol and free fatty acid release) was measured in perifused adipocytes. Intra‐abdominal fat in PFK‐M–deficient female mice (5–10 months old) was 17 ± 3% of that of wild‐type littermates (n = 4; P < 0.02). Epididymal fat weight in 15 animals (7–9.5 months) was 34 ± 4% of control littermate (P < 0.002), with 10–30% lower body weight. Basal and insulin‐stimulated lipogenesis in PFK‐M–deficient epididymal adipocytes was 40% of the rates in cells from heterozygous littermates (n = 3; P < 0.05). The rate of isoproterenol‐stimulated lipolysis in wild‐type adipocytes declined ～10% after 1 h and 50% after 2 h; in PFK‐M–deficient cells it declined much more rapidly, 50% in 1 h and 90% in 2 h, and lipolytic oscillations appeared to be damped (n = 4). These results indicate an important role for PFK‐M in adipose metabolism. This may be related to the ability of this isoform to generate glycolytic oscillations, because such oscillations may enhance the production of the triacylglycerol precursor α‐glycerophosphate.     

Adipose Angiotensinogen Secretion,Blood Pressure,and AGT M235T Polymorphism in Obese Patients

Objective: To investigate AGT secretion in cultured adipocytes from obese patients and its relationship with obesity‐related phenotypes, blood pressure, and the M235T polymorphism in the AGT gene. Research Methods and Procedures: Measurements, including anthropometry, body composition (DXA), and blood pressure, were performed in 61 overweight or obese women (BMI: 28 to 68 kg/m²). A subcutaneous abdominal adipose tissue biopsy was used for adipocyte size determination and quantification of AGT secretion in the medium of cultured adipocytes. AGT M235T genotype was determined using polymerase chain reaction‐restriction fragment length polymorphism. Results: Adipose secretion of the AGT protein (range, 140 to 2575 ng/10⁶ cells/24 h) was not significantly correlated with BMI, body fat, or blood pressure and did not vary according to the M235T polymorphism in the AGT gene. However, the AGT M235T polymorphism was associated with adipocyte size (111.6 ± 2.8, 108.8 ± 1.9, 118.2 ± 2.6 μm in MM, MT, and TT genotypes, respectively; p < 0.01) after adjustment for age and fat mass. An association between the AGT M235T polymorphism and adipocyte size (p < 0.02 adjusted for sex, age, and BMI) was found in another independent sample of 106 obese subjects (sex ratio, M/F 16/90; BMI, 29 to 70 kg/m²). Discussion: In cultured adipocytes from obese subjects, AGT secretion was not associated with body fat phenotypes, blood pressure, or fat cell size. However, results from two independent studies suggest an association between the AGT M235T polymorphism and adipocyte size.     

Relationship of Body Composition to Body‐Fatness Estimation in Japanese University Students

Objective: To examine the relationship between self‐estimated whole body size and fatness and whole body and regional composition, and the relationship between self‐estimated whole body fatness and self‐estimated regional fatness in Japanese university students. Research Methods and Procedures: This was a cross‐sectional study using Japanese university students (110 men and 79 women). The percentage of body fat, fat mass (FM), and fat‐free mass (FFM) were measured by underwater weighing and used as body composition variables. Subcutaneous fat thicknesses were determined at seven sites by ultrasonography to estimate regional body composition, and six circumferences and four breadths to estimate regional size. Relative body size and fatness were self‐estimated using a questionnaire. Results: Only women tended to estimate themselves as being fatter than they actually were. Self‐estimated body fatness moderately correlated with the percentage of body fat (men, r = 0.41; women, r = 0.40) FM (men, r = 0.50; women, r = 0.51), and body mass index (r = 0.56 for men and 0.56 for women). After adjusting for the percentages of body fat and FM, self‐estimated fatness correlated with body mass index (r = 0.31 for men and r = 0.37 for women). Among self‐estimated regional fatness, self‐estimated abdominal fatness had the strongest correlation with self‐estimated whole body fatness in both genders. Discussion: The low correlation between estimated and actual body fatness in both genders indicates that Japanese university students, especially women, inaccurately estimate their percentage of body fat. In fact, both men and women primarily estimate their whole body fatness by body weight relative to height.     

Rapamycin Inhibits Human Adipocyte Differentiation in Primary Culture

Objective: The immunosuppressant drug rapamycin, has been reported to inhibit 3T3‐L1 adipocyte differentiation by interfering with critical postconfluent mitoses that are required early on for successful differentiation of this cell line (clonal expansion phase). In contrast to the murine 3T3‐L1 preadipocyte cell line, human preadipocytes in primary culture do not undergo clonal expansion during differentiation. We investigated whether rapamycin could inhibit human adipocyte differentiation. Research Methods and Procedures: The effect of rapamycin on the induction of differentiation of human preadipocytes in primary culture into adipocytes was measured using Oil Red O staining and glycerol phosphate dehydrogenase activity. Results: We have observed that rapamycin severely curtails human adipocyte differentiation of both omental and abdominal subcutaneous preadipocytes (to 14% and 19% of standard differentiation, respectively). The rapamycin‐mediated inhibition of human adipocyte differentiation could be reversed in the presence of excess amounts of FK‐506, which displaces rapamycin from its intracellular receptor, FKPB12. Measurement of cytosolic protein and [³H]thymidine incorporation into DNA confirmed the absence of proliferation during differentiation of human preadipocytes in primary culture. Discussion: Our data indicate that rapamycin exerts important negative regulatory effects on adipogenesis in human preadipocytes, through a mechanism that does not depend on interruption of clonal expansion.     

Inflammation and Race and Gender Differences in Computerized Tomography‐measured Adipose Depots

A growing body of evidence has consistently shown a correlation between obesity and chronic subclinical inflammation. It is unclear whether the size of specific adipose depots is more closely associated with concentrations of inflammatory markers than overall adiposity. This study investigated the relationship between inflammatory markers and computerized tomography‐derived abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat in older white and black adults. Data were from 2,651 black and white men and women aged 70–79 years participating in the Health, Aging, and Body Composition (Health ABC) study. Inflammatory markers, interleukin‐6 (IL‐6), C‐reactive protein (CRP), and tumor necrosis factor‐α (TNF‐α) were obtained from serum samples. Abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were quantified on computerized tomography images. Linear regression analysis was used to evaluate the cross‐sectional relationship between specific adipose depots and inflammatory markers in four race/gender groups. As expected, blacks have less visceral fat than whites and women less visceral fat than men. However, abdominal visceral adiposity was most consistently associated with significantly higher IL‐6 and CRP concentrations in all race/gender groups (P < 0.05), even after controlling for general adiposity. Thigh intermuscular fat had an inconsistent but significant association with inflammation, and there was a trend toward lower inflammatory marker concentration with increasing thigh subcutaneous fat in white and black women. Despite the previously established differences in abdominal fat distribution across gender and race, visceral fat remained a significant predictor of inflammatory marker concentration across all four subgroups examined.