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.     

Comparison of methods for assessing abdominal adipose tissue from magnetic resonance images

Objective: To compare the inter‐rater and intra‐rater reliability and analysis time of two methods for quantifying visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes from magnetic resonance (MR) images. Research Methods and Procedures: Ten subjects (BMI, 27.0 ± 2.1 kg/m²; 56 years of age ± 4 years) underwent MR imaging of the abdomen. Ten transverse T1‐weighted images were selected from each scan and analyzed using two software packages that differ in principle. The first method, ANALYZE version 5.0, represents the manual threshold method, and the second, HIPPO version 1.3, is based on the fuzzy clustering approach. Inter‐rater reliability for each method was assessed by comparing the intra‐class correlation coefficients (ICCs) for VAT and SAT results from two evaluators, and intra‐rater reliability for each method was assessed by comparing ICCs for VAT and SAT analyses performed 1 week apart by the same evaluator. The total time for analysis also was compared between methods. Results: The inter‐rater reliability for VAT was greater with HIPPO than with ANALYZE (ICC = 0.996 vs. 0.828), whereas inter‐rater reliability for SAT did not differ between methods (ICC = 0.975 and 0.987). The intra‐rater reliability was equally high with HIPPO and ANALYZE for both VAT (ICC = 0.998 vs. 0.992) and SAT (ICC = 0.996 vs. 0.992). HIPPO required less than one‐half as much analysis time as ANALYZE (15.9 ± 4.4 vs. 36.5 ± 8.2 minutes, p < 0.0001). Discussion: HIPPO software appears advantageous for the quantification of VAT from multislice MR images because inter‐rater results are more reliable, and it is more time‐efficient than less automated methods.     

Regional Intra‐Subject Variability in Abdominal Adiposity Limits Usefulness of Computed Tomography

Objective: Computed tomography (CT) and magnetic resonance imaging, the most accurate methods of abdominal fat measurement, have been applied using a number of protocols, ranging from single‐slice area determination to multiple‐slice volume calculation. The aim of this study was to assess the validity of single‐slice CT for abdominal fat area measurement by estimating the intra‐subject variability in abdominal fat areas and comparing the ranking of subjects across four contiguous abdominal levels. Research Methods and Procedures: Nineteen premenopausal women (age, 35.3 ± 1.4 years; mean ± SE) were studied. CT was used to measure intra‐abdominal fat (IAF) area, percentage of total intra‐abdominal area (%IAF), subcutaneous abdominal fat (SAF) area, and IAF/SAF at four adjacent cross‐sectional lumbar levels (L2–L4). Intra‐subject variability (percentage) was defined as SD/mean × 100. Total body fat was measured by DXA, which was further analyzed for central abdominal fat. Results: Mean body mass index was 24.9 ± 1.0 kg/m². The average (range) intra‐subject variability was 28% (8% to 61%) for IAF, 46% (19% to 124%) for %IAF, 26% (14% to 38%) for SAF area, and 19% (7% to 71%) for IAF/SAF. The pattern of this variability was not uniform between subjects, because their ranking by IAF area was markedly different at each CT level. Discussion: We demonstrated significant intra‐subject variability in CT‐measured adipose tissue areas across four predetermined sites. This resulted in a difference in the ordering of subjects by IAF at each of the four imaging sites, suggesting that the usefulness of single‐slice CT in the assessment of abdominal adiposity in premenopausal women may be limited, particularly when performed for the purpose of making comparisons between subjects based on abdominal fat area.     

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.     

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.     

Association of Physical Activity and Visceral Adipose Tissue in Older Women and Men

Objective: Physical inactivity, abdominal fat, and age are known risk factors for diabetes, cardiovascular disease, and certain cancers. Previous evidence supports an inverse relationship between physical activity (PA) and abdominal fat estimated by waist circumference. However, few investigations used computed tomography (CAT) scanning for precise measures of abdominal fat. Research Methods and Procedures: Sixty-five female and 106 male (age, 64.5 ± 5.2 years) participants in the Prostate, Lung, Colon and Ovarian Cancer Screening Trial underwent a cross-sectional L4–L5 CAT scan to differentiate visceral adipose tissue (VAT). Subjects were also interviewed by phone to determine PA and physical difficulties (PD). Results: Women had lower VAT (170 ± 84 vs. 205 ± 95 cm², p = 0.014), lower VAT/total fat (29.9 ± 7.2% vs. 42.6 ± 10.2%, p < 0.001), and higher total fat (596 ± 385 vs. 482 ± 183 cm², p = 0.010) than men. PA was inversely correlated to VAT (r = −0.164, p = 0.034) and total fat (r = −0.231, p = 0.003) in men and women. Those who reported a PD had higher VAT (249 vs. 180 cm², p < 0.001) and total fat (652 vs. 500 cm², p = 0.008). Multiple regression analysis indicated total PA and PD were independently associated to VAT and total fat. Discussion: This investigation suggests a beneficial effect of PA and a negative influence of PD on abdominal fat accumulation. Although the cross-sectional design limits cause-effect designations, these results are consistent with other studies showing PA/abdominal fat relation.     

Increased Whole‐Body Adiposity Without a Concomitant Increase in Liver Fat is Not Associated With Augmented Metabolic Dysfunction

Aim of this study was to determine whether an increase in adiposity, without a concomitant increase in intrahepatic triglyceride (IHTG) content, is associated with a deterioration in metabolic function. To this end, multiorgan insulin sensitivity, assessed by using a two‐stage hyperinsulinemic–euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusion, and very low‐density lipoprotein (VLDL) kinetics, assessed by using stable isotopically labeled tracer infusion and mathematical modeling, were determined in 10 subjects with class I obesity (BMI: 31.6 ± 0.3 kg/m²; 37 ± 2% body fat; visceral adipose tissue (VAT): 1,225 ± 144 cm³) and 10 subjects with class III obesity (BMI: 41.5 ± 0.5 kg/m²; 43 ± 2% body fat; VAT: 2,121 ± 378 cm³), matched on age, sex, and IHTG content (14 ± 4 and 14 ± 3%, respectively). No differences between class I and class III obese groups were detected in insulin‐mediated suppression of palmitate (67 ± 3 and 65 ± 3%, respectively; P = 0.635) and glucose (67 ± 3 and 73 ± 5%, respectively; P = 0.348) rates of appearance in plasma, and the insulin‐mediated increase in glucose disposal (218 ± 18 and 193 ± 30%, respectively; P = 0.489). In addition, no differences between class I and class III obese groups were detected in secretion rates of VLDL‐triglyceride (6.5 ± 1.0 and 6.0 ± 1.4 µmol/l·min, respectively; P = 0.787) and VLDL‐apolipoprotein B‐100 (0.40 ± 0.05 and 0.41 ± 0.04 nmol/l·min, respectively; P = 0.866), and plasma clearance rates of VLDL‐triglyceride (31 (16–59) and 29 (18–46) ml/min, respectively; P = 0.888) and VLDL‐apolipoprotein B‐100 (15 (11–19) and 17 (11–25) ml/min, respectively; P = 0.608). We conclude that increased adiposity without a concomitant increase in IHTG content does not cause additional abnormalities in adipose tissue, skeletal muscle, and hepatic insulin sensitivity, or VLDL metabolism.     

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.     

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.     

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.     

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.     

Genome‐wide Association Study and Follow‐up Analysis of Adiposity Traits in Hispanic Americans: The IRAS Family Study

We investigated candidate genomic regions associated with computed tomography (CT)–derived measures of adiposity in Hispanics from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS). In 1,190 Hispanic individuals from 92 families 3 from the San Luis Valley, Colorado and San Antonio, Texas, we measured CT‐derived visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral:subcutaneous ratio (VSR). A genome‐wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (～317K single‐nucleotide polymorphisms (SNPs)) in 229 individuals from the San Antonio site (stage 1). In total, 297 SNPs with evidence for association with VAT, SAT, or VSR, adjusting for age and sex (P < 0.001), were genotyped in the remaining 961 Hispanic samples. The entire Hispanic cohort (n = 1,190) was then tested for association, adjusting for age, sex, site of recruitment, and admixture estimates (stage 2). In stage 3, additional SNPs were genotyped in four genic regions showing evidence of association in stage 2. Several SNPs were associated in the GWAS (P < 1 × 10^?5) and were confirmed to be significantly associated in the entire Hispanic cohort (P < 0.01), including: rs7543757 for VAT, rs4754373 and rs11212913 for SAT, and rs4541696 and rs4134351 for VSR. Numerous SNPs were associated with multiple adiposity phenotypes. Targeted analysis of four genes whose SNPs were significant in stage 2 suggests candidate genes for influencing the distribution (RGS6) and amount of adiposity (NGEF). Several candidate loci, including RGS6 and NGEF, are associated with CT‐derived adipose fat measures in Hispanic Americans in a three‐stage genetic association study.     

Ethnic and sex differences in visceral,subcutaneous, and total body fat in children and adolescents

Objective: This study investigated ethnic and sex differences in the distribution of fat during childhood and adolescence. Design and Methods : A cross‐sectional sample (n = 382), aged 5–18 years, included African American males (n = 84), White males (n = 96), African American females (n = 118), and White females (n = 84). Measures for total body fat (TBF) mass and abdominal adipose tissue (total volume and L4‐L5 cross‐sectional area) for both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depots were assessed by dual‐energy X‐ray absorptiometry and magnetic resonance image, respectively. Analyses of covariance (ANCOVAs) were used to determine ethnic and sex differences in TBF (adjusted for age) and ethnic and sex differences in SAT and VAT (adjusted for both age and TBF). Results: Age‐adjusted TBF was greater in African Americans (P = 0.017) and females (P < 0.0001) compared with Whites and males, respectively. In age‐ and TBF‐adjusted ANCOVAs, no differences were found in the SAT. The VAT volume was, however, greater in Whites (P < 0.0001) and males (P < 0.0001) compared with African Americans and females, respectively. Similar patterns were observed in SAT and VAT area at L4‐L5. Conclusions: The demonstrated ethnic and sex differences are important confounders in the prevalence of obesity and in the assignment of disease risk in children and adolescents.     

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.     

Breast Volume is an Independent Predictor of Visceral and Ectopic Fat in Premenopausal Women

It is suggested that a large breast size among women may predict type 2 diabetes risk independent of BMI and waist circumference (WC). The purpose of this study was to determine the independent associations of breast volume with cardiometabolic risk factors and regional fat distribution. A total of 92 overweight or obese premenopausal women (age = 39.9 ± 6.8 years) underwent full‐body magnetic resonance imaging (MRI) for the assessment of breast volume, visceral adipose tissue (VAT), abdominal and lower‐body subcutaneous AT (SAT), and intermuscular AT (IMAT), a 2‐h oral glucose tolerance test (OGTT), and fasting phlebotomy for assessment of triglyceride, total, high‐density lipoprotein–, and low‐density lipoprotein–cholesterol levels. Breast volume was not associated with any of the cardiometabolic risk factors assessed (P > 0.05). However, VAT was consistently associated with a number of cardiometabolic risk factors (OGTT glucose, OGTT insulin, and triglyceride levels) after controlling for age, BMI, WC, breast volume, and the other AT depots. In univariate models, breast volume was positively associated with VAT, IMAT, and abdominal and lower‐body SAT (P < 0.05). After controlling for age, BMI, and WC level, breast volume remained positively associated with VAT and IMAT (P < 0.05), such that women with the highest breast volume had ～1.1 and 1.3 kg more VAT and IMAT, respectively, but no more abdominal or lower‐body SAT, by comparison to women with the smallest breast volume. Thus, the previously documented association between breast size and type 2 diabetes risk may be in part explained by excess VAT and/or IMAT deposition.     

Adipose tissue‐specific modulation of galectin expression in lean and obese mice: Evidence for regulatory function

Objective:

Galectins (Gal) exert many activities, including regulation of inflammation and adipogenesis. We evaluated modulation of Gal‐1, ‐3, ‐9 and ‐12 in visceral (VAT) and subcutaneous (SAT) adipose tissue in mice.

Design and Methods:

We used two mouse models of obesity, high‐fat diet induced obesity (DIO) and ob/ob mice. We also evaluated the response of Gal‐1 KO mice to DIO.

Results:

Both age and diet modulated expression of galectins, with DIO mice having higher serum Gal‐1 and Gal‐3 versus lean mice after 13‐17 weeks of high‐fat diet. In DIO mice there was a progressive increase in expression of Gal‐1 and Gal‐9 in SAT, whereas Gal‐3 increased in both VAT and SAT. Expression of Gal‐12 declined over time in VAT of DIO mice, similar to adiponectin. Obesity lead to increased production of Gal‐1 in adipocytes, whereas the increased Gal‐3 and Gal‐9 of obesity mostly derived from the stromovascular fraction. Expression of Gal‐12 was restricted to adipocytes. There was increased production of Gal‐3 and Gal‐9, but not Gal‐1, in CD11c^? and CD11c⁺ macrophages from VAT of DIO versus lean mice. Expression of Gal‐1, ‐3 and ‐12 in VAT and SAT of ob/ob mice followed a trend comparable to DIO mice. Rosiglitazone reduced serum Gal‐1, but not Gal‐3 and modulated expression of Gal‐3 in VAT and Gal‐9 and Gal‐12 in SAT of DIO mice. High‐fat feeding lead to increased adiposity in Gal‐1 KO versus WT mice, with loss of correlation between leptin and adiposity and no alterations in glucose and insulin levels.

Conclusions:

Obesity leads to differential modulation of Gal‐1, 3, 9 and 12 in VAT and SAT, with Gal‐1 acting as a modulator of adiposity.

     

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.     

Measurement Site and the Association Between Visceral and Abdominal Subcutaneous Adipose Tissue With Metabolic Risk in Women

The associations between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) and metabolic risk may be influenced by measurement site. The aim of this study was to compare the strength of the associations between VAT and ASAT, as assessed by a cross‐sectional image (area) or total volume, and prevalent metabolic syndrome (MetS). We also examined the association between changes in abdominal AT area and volume with concomitant changes in metabolic risk. Abdominal AT volume and areas were derived using ～35 continuous computed tomography (CT) images from T10–T11 to L5–S1 in overweight or obese postmenopausal women before (n = 67) and after (n = 39) a 6‐month exercise intervention. At baseline, measurement site did not influence the inter‐relationship between ASAT area and total volume, and between ASAT and MetS. Conversely, VAT areas at L1–L2 and L2–L3 were stronger correlates of VAT volume at baseline (L1–L2 (r = 0.94), L2–L3 (r = 0.95), L4–L5 (r = 0.89)) and changes therein (L1–L2 (r = 0.77), L2–L3 (r = 0.75), L4–L5 (r = 0.55)) as compared to L4–L5, but were not significantly better predictors of MetS as compared to L4–L5 or the total volume (L2–L3: odds ratio (OR) = 2.68 (1.6–4.4), L1–L2: OR = 1.88 (1.2–3.0), L4–L5: OR = 2.56 (1.6–4.1), volume: OR = 2.07 (1.1–3.8)). Changes in VAT and ASAT were not associated with changes in MetS (P > 0.10). Although measurement site has an impact on the prediction of VAT volume, this does not translate into an improved prediction for the MetS. Thus, there is not enough evidence to support changing the current research practice of assessing VAT volume or at L4–L5 for the prediction of metabolic risk.     

The Human Visceral Fat Depot Has a Unique Inflammatory Profile

Obesity can be considered as a low‐grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity‐associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3±5.5 kg/m²) were included in the study. Body fat (dual‐energy X‐ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation‐related differences in gene expression (real‐time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation, while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01) expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.     

Visceral and Subcutaneous Adiposity and Brachial Artery Vasodilator Function

Endothelial dysfunction may link obesity to cardiovascular disease (CVD). We tested the hypothesis that visceral abdominal tissue (VAT) as compared with subcutaneous adipose tissue (SAT) is more related to endothelium‐dependent vasodilation. Among Framingham Offspring and Third Generation cohorts (n = 3,020, mean age 50 years, 47% women), we used multivariable linear regression adjusted for CVD and its risk factors to relate computed tomography (CT)‐assessed VAT and SAT, BMI, and waist circumference (WC), with brachial artery measures. In multivariable‐adjusted models, BMI, WC, VAT, and SAT were positively related to baseline artery diameter and baseline mean flow velocity (all P < 0.001), but not hyperemic mean flow velocity. In multivariable‐adjusted models, BMI (P = 0.002), WC (P = 0.001), and VAT (P = 0.01), but not SAT (P = 0.24) were inversely associated with percentage of flow‐mediated dilation (FMD%). However, there was little incremental increase in the proportion of variability explained by VAT (R² = 0.266) as compared to SAT (R² = 0.265), above and beyond traditional risk factors. VAT, but not SAT was associated with FMD% after adjusting for clinical covariates. Nevertheless, the differential association with VAT as compared to SAT was minimal.