DPP4 Gene DNA Methylation in the Omentum is Associated With Its Gene Expression and Plasma Lipid Profile in Severe Obesity

Severely obese subjects with the metabolic syndrome (MS) have higher dipeptidyl peptidase‐4 (DPP4) expression in their visceral adipose tissue (VAT) compared to obese individuals without MS. We tested the hypothesis that methylation level of CpG sites in the DPP4 promoter CpG island in VAT was genotype‐dependent and associated with DPP4 mRNA abundance and MS‐related phenotypes. The VAT DNA was extracted in 92 severely obese premenopausal women undergoing biliopancreatic derivation for the treatment of obesity. Women were nondiabetic and none of them used medication to treat MS features. Cytosine methylation rates (%) of 102 CpG sites in the DPP4 CpG island were assessed by pyrosequencing of sodium bisulfite‐treated DNA. Methylation rates were >10% for CpG sites 94–102. Their mean methylation rate (%Meth_94–102) was different between genotypes for DPP4 polymorphisms rs13015258 (P = 0.001), rs17848915 (P = 0.0004), and c.1926 G>A (P = 0.001). The %Meth_94–102 correlated negatively with DPP4 mRNA abundance (r = ?0.25, P < 0.05) and positively with plasma high‐density lipoprotein (HDL) cholesterol concentrations (r = 0.22, P < 0.05), whereas DPP4 mRNA abundance correlated positively with plasma total‐/HDL‐cholesterol ratio (r = 0.25; P < 0.05). In the VAT of nondiabetic severely obese women, genotype‐dependent methylation levels of specific CpG sites in the DPP4 promoter CpG island were associated with DPP4 gene expression and variability in the plasma lipid profile. Higher DPP4 gene expression in VAT and its relationship with the plasma lipid profile may be explained by actually unknown DPP4 biological effect or, to another extent, may also be a marker of VAT inflammation known to be associated with metabolic disturbances.     

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.     

The Gene Expression of the Main Lipogenic Enzymes is Downregulated in Visceral Adipose Tissue of Obese Subjects

Contradictory findings regarding the gene expression of the main lipogenic enzymes in human adipose tissue depots have been reported. In this cross‐sectional study, we aimed to evaluate the mRNA expression of fatty acid synthase (FAS) and acetyl‐CoA carboxilase (ACC) in omental and subcutaneous (SC) fat depots from subjects who varied widely in terms of body fat mass. FAS and ACC gene expression were evaluated by real time‐PCR in 188 samples of visceral adipose tissue which were obtained during elective surgical procedures in 119 women and 69 men. Decreased sex‐adjusted FAS (?59%) and ACC (?49%) mRNA were found in visceral adipose tissue from obese subjects, with and without diabetes mellitus type 2 (DM‐2), compared with lean subjects (both P < 0.0001). FAS mRNA was also decreased (?40%) in fat depots from overweight subjects (P < 0.05). Indeed, FAS mRNA was significantly and positively associated with ACC gene expression (r = 0.316, P < 0.0001) and negatively with BMI (r = ?0.274), waist circumference (r = ?0.437), systolic blood pressure (r = ?0.310), serum glucose (r = ?0.277), and fasting triglycerides (r = ?0.226), among others (all P < 0.0001). Similar associations were observed for ACC gene expression levels. In a representative subgroup of nonobese (n = 4) and obese women (n = 6), relative FAS gene expression levels significantly correlated (r = 0.657, P = 0.034; n = 10) with FAS protein values. FAS protein levels were also inversely correlated with blood glucose (r = ?0.640, P = 0.046) and fasting triglycerides (r = ?0.832, P = 0.010). In conclusion, the gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue from obese subjects.     

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.     

Apolipoprotein A‐II Polymorphism and Visceral Adiposity in African‐American and White Women

To determine the association between the ?265 T to C substitution in the apolipoprotein A‐II (APOA‐II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African‐American and white women, we genotyped 237 women (115 African‐American and 122 white) for this polymorphism. Body composition was assessed by DXA, and VAT was determined from a single computed tomography scan. In addition to VAT, we examined the association between the polymorphism and other phenotypes (total body fat, total abdominal adipose tissue, and subcutaneous abdominal adipose tissue). The mutant C allele in the APOA‐II gene was less frequent in African‐American compared with white women, 23% vs. 36%, respectively (p < 0.01). VAT was significantly higher in carriers of the C allele compared with noncarriers after adjustment for total body fat (p < 0.05). When separate analyses by ethnic group were conducted, the association between the polymorphism and VAT was observed in white (p < 0.05) but not African‐American (p = 0.57) women. There was no association between the polymorphism and the other phenotypes. These results indicate a significant association between the T265C APOA‐II polymorphism and levels of VAT in premenopausal women. This association is present in white but not African‐American women.     

Relation of epicardial fat and alanine aminotransferase in subjects with increased visceral fat

Background: Increased visceral adipose tissue (VAT) is a risk factor for an unfavorable cardio‐metabolic profile and fatty liver. Individuals with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) can be associated with metabolic syndrome (MS) and higher visceral fat. However, the potential link between cardiac adiposity, emerging index of visceral adiposity, and fatty liver is still unexplored. Objective: To evaluate whether echocardiographic epicardial adipose tissue, index of cardiac adiposity, could be related to serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, surrogate markers of fatty liver, in HIV‐infected patients with (HIV+MS+) and without HAART‐associated MS (HIV+MS‐). Methods and Procedures: This was a cross‐sectional observational study on 57 HIV+MS+ patients, 52 HIV+MS? and 57 HIV‐negative subjects with MS (HIV?MS+), as control group. Epicardial fat thickness and intra‐abdominal VAT were obtained by echocardiography and magnetic resonance imaging (MRI), respectively. Serum ALT and AST activity, plasma adiponectin levels, and MS biochemical parameters were measured. Results: Echocardiographic epicardial fat thickness was correlated with MRI‐VAT (r = 0.83, P < 0.01), AST/ALT ratio (r = 0.77, P < 0.01), ALT (r = 0.58, P < 0.01), AST (r = 0.56, P < 0.01), and adiponectin (r = ?0.45, P < 0.01) in HIV+MS+. MRI‐VAT and AST/ALT ratio were the best correlates of epicardial fat thickness (r ² = 0.45, P < 0.01). Discussion: This study shows for the first time a clear relationship of epicardial fat, index of cardiac and visceral adiposity, and serum ALT and AST activity, markers of fatty liver, in subjects with increased visceral adiposity and cardio‐metabolic risk. This correlation seems to be independent of overall adiposity and rather function of excess visceral adiposity.     

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.     

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.     

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

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

Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism

Objective: To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy. Research Methods and Procedures: We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity‐related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study. Results: The strongest results were generation‐specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These associations remained significant after adjusting for multiple testing. Several other associations between body composition measures and the IVS18 + 181C>T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships. Discussion: These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity‐related phenotypes potentially in an age‐dependent manner.     

Dysregulation of the Autonomic Nervous System Can Be a Link between Visceral Adiposity and Insulin Resistance

Objective: To evaluate the interplay among abdominal adipose tissue distribution, the cortisol axis, the autonomic nervous system, and insulin resistance. Research Methods and Procedures: Two age‐, sex‐, and BMI‐matched groups were studied. Fifteen subjects were first‐degree relatives of patients with type 2 diabetes (R), and 15 had no family history of diabetes (controls, C). A hyperinsulinemic euglycemic clamp, cortisol measurements, and analysis of heart rate variability (HRV) were performed. Computed tomography was performed in a subgroup (n = 9 + 9) to determine abdominal adipose tissue distribution. Results: R tended to be less insulin‐sensitive than C (M value 9.2 ± 1.0 vs 10.3 ± 0.7 mg/kg per minute, not significant). Stimulation with tetracosactin or corticotropin releasing hormone yielded lower peak serum cortisol levels in R (p = 0.03 and p = 0.06, respectively). The amount of visceral abdominal fat (VAT) tended to be greater in R. In all subjects, VAT was negatively correlated to insulin sensitivity (r = ?0.93, p < 0.001). There was a positive association between VAT and resting heart rate (r = 0.70, p = 0.003) and sympathetic/parasympathetic ratio in HRV assessment after tilt (r = 0.53, p = 0.03). Subcutaneous abdominal tissue was not associated with insulin sensitivity or any of the hormonal or HRV assessments. Discussion: Subjects genetically predisposed for type 2 diabetes had a tendency toward a larger amount of VAT and to lower insulin sensitivity compared with control subjects. The amount of visceral fat was strongly associated with insulin resistance and signs of a high ratio of sympathetic vs. parasympathetic reactivity. A large amount of visceral fat may act in concert with sympathetic/parasympathetic imbalance to promote the development of insulin resistance, and this may be partly independent of genetic background.     

LMNA mRNA expression is altered in human obesity and type 2 diabetes

Objective: The aim of this study was to analyze lamin A/C mRNA levels in abdominal subcutaneous adipose tissue in two conditions—obesity and type 2 diabetes—that share common inflammatory and metabolic features, and to assess their relationship with selected inflammatory and adipogenic genes. Methods and Procedures: This is a cross‐sectional study involving 52 nondiabetic and 54 type 2 diabetes patients. Anthropometrical and analytical measurements (glycemic, lipidic, and inflammatory profiles) were performed, and mRNA expression was determined using real‐time PCR. Results: Lamin A and C isoforms are expressed differentially. Lamin A/C mRNA levels were increased in obese and in type 2 diabetes patients. We also observed a strong relationship between both isoforms (B = 2.218, P < 0.001) and among lamin C mRNA expression and adipogenic (sterol‐responsive element binding protein‐1 (SREBP1c)) and inflammatory (interleukin‐6 (IL‐6)) markers (B = 0.854, P = 0.001, and B = 0.557, P < 0.001, respectively). Discussion: These data suggest that lamin A/C may be involved in the adipocyte gene profile observed in obesity and type 2 diabetes.     

Monocyte chemoattractant protein-1 in obesity and type 2 diabetes. Insulin sensitivity study

Objective: Our goal was to test any association between human plasma circulating levels of monocyte chemoattractant protein‐1 (cMCP‐1) and insulin resistance and to compare monocyte chemoattractant protein‐1 (MCP‐1) adipose tissue gene expression and cMCP‐1 in relation with inflammatory markers. Research Methods and Procedures: cMCP‐1 was measured in n = 116 consecutive control male subjects to whom an insulin sensitivity (S_i) test was performed. Circulating levels of soluble CD14, soluble tumor necrosis factor receptor type 2 (sTNFR2), soluble interleukin‐6 (sIL‐6), and adiponectin also were measured. Subcutaneous adipose tissue samples were obtained from n = 107 non‐diabetic and type 2 diabetic subjects with different degrees of obesity. Real‐time polymerase chain reaction was used to measure gene expression of MCP‐1, CD68, tumor necrosis factor‐α (TNF‐α), and its receptor TNFR2. Results: In the S_i study, no independent effect of cMCP‐1 levels on insulin sensitivity was observed. In the expression study, in non‐diabetic subjects, MCP‐1 mRNA had a positive correlation with BMI (r = 0.407, p = 0.003), TNF‐α mRNA (r = 0.419, p = 0.002), and TNFR2 mRNA (r = 0.410, p = 0.003). In these subjects, cMCP‐1 was found to correlate with waist‐to‐hip ratio (r = 0.322, p = 0.048). In patients with type 2 diabetes, MCP‐1 mRNA was up‐regulated compared with non‐diabetic subjects. TNF‐α mRNA was found to independently contribute to MCP‐1 mRNA expression. In this group, CD68 mRNA was found to correlate with BMI (r = 0.455, p = 0.001). Discussion: cMCP‐1 is not associated with insulin sensitivity in apparently healthy men. TNF‐α is the inflammatory cytokine associated with MCP‐1 expression in subcutaneous adipose tissue.     

A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals

A previous expression profiling of visceral adipose tissue (VAT) revealed that the immune response gene interferon-gamma-inducible protein 30 (IFI30) gene was 1.72-fold more highly expressed in non-diabetic severely obese men with the metabolic syndrome as compared to those without. Given the importance of low-grade inflammation in obesity-related metabolic complications, we hypothesized that variants in the IFI30 gene are associated with cardiovascular disease (CVD) risk factors. A detailed genetic investigation was performed at the IFI30 locus by sequencing its promoter, exons and intron–exon junction boundaries using DNA of 25 severely obese men. Among the 21 sequence-derived single-nucleotide polymorphisms (SNPs), 5 tagged SNPs (covering 100% of the common SNPs identified) were genotyped in two independent samples of severely obese patients (total n = 1,283). Using a multistage experimental design, chi-square analyses and logistic regressions were performed to compare genotype frequencies and compute odds-ratios (OR) for low and high CVD risk groups (dyslipidemia, hyperglycemia/diabetes and hypertension). A significant association was observed with the non-synonymous SNP rs11554159 (p.R76Q), where GA individuals showed lower risk (OR = 0.67; P = 0.0009) for hyperglycemia/diabetes as compared to homozygotes for the major allele (GG). No association was observed between rs11554159 and VAT IFI30 mRNA levels (P = 0.81), and the expression levels were not correlated with fasting plasma glucose levels (P = 0.31) in 112 non-diabetic severely obese women. The localization of rs11554159 near the active site of IFI30 suggests a functional effect of this SNP. This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals.     

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

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

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.     

A role of lipin in human obesity and insulin resistance: relation to adipocyte glucose transport and GLUT4 expression

The mouse lipin gene, Lpin1, is important for adipose tissue development and is a candidate gene for insulin resistance. Here, we investigate the adipose tissue expression levels of the human LPIN1 gene in relation to various clinical variables as well as adipocyte function. LPIN1 gene expression was induced at an early step in human preadipocyte differentiation in parallel with peroxisome proliferator-activated receptor gamma. Lipin mRNA levels were higher in fat cells than in adipose tissue segments but showed no difference between subcutaneous and omental depots. Moreover, LPIN1 expression levels were reduced in obesity, improved following weight reduction in obese subjects, and were downregulated in women with the metabolic syndrome. With respect to adipocyte function, adipose LPIN1 gene expression was strongly associated with both basal and insulin-mediated subcutaneous adipocyte glucose transport as well as mRNA levels of glucose transporter 4 (GLUT4). We show that body fat accumulation is a major regulator of human adipose LPIN1 expression and suggest a role of LPIN1 in human preadipocyte as well as mature adipocyte function.     

Elevated Systemic Hepcidin and Iron Depletion in Obese Premenopausal Females

Hepcidin, the body's main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = ?0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = ?0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = ?0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was ～700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin‐mediated inhibition of dietary iron absorption.     

Dietary patterns,abdominal visceral adipose tissue,and cardiometabolic risk factors in African Americans: The Jackson heart study

Objective:

To examine the relative association of abdominal visceral adipose tissue (VAT) with cardiometabolic risk factors between African and European Americans.

Design and Methods:

We conducted a cross‐sectional study of 2035 African Americans from Jackson Heart Study (JHS) and 3170 European Americans from Framingham Heart Study (FHS) who underwent computed tomography assessment of VAT and subcutaneous adipose tissue (SAT). The FHS participants were weighted to match the age distribution of the JHS participants and the metabolic risk factors were examined by study groups in relation to VAT.

Results:

JHS participants had higher rates of obesity, hypertension, diabetes and metabolic syndrome than FHS participants (all p = 0.001). The associations were weaker in JHS women for VAT with blood pressure, triglycerides, HDL‐C, and total cholesterol (p_interaction = 0.03 to 0.001) than FHS women. In contrast, JHS men had stronger associations for VAT with high triglycerides, low HDL, and metabolic syndrome (all p_interaction = 0.001) compared to FHS men. Similar associations and gender patterns existed for SAT with most metabolic risk factors.

Conclusions:

The relative association between VAT and cardiometabolic risk factors is weaker in JHS women compared to FHS women, whereas stronger association with triglycerides and HDL were observed in JHS men.