Subcutaneous Fat Shows Higher Thyroid Hormone Receptor‐α1 Gene Expression Than Omental Fat

The aims of this work were to evaluate thyroid hormone receptor‐α (TRα), TRα1, and TRα2 mRNA gene expression and TRα1:TRα2 ratio, identified as candidate factors for explaining regional differences between human adipose tissue depots. TRα, TRα1, and TRα2 mRNA levels, and the gene expressions of arginine–serine‐rich, splicing factor 2 (SF2), heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), and Spot 14 (S14) were evaluated in 76 paired adipose tissue samples obtained from a population of 38 women who varied widely in terms of obesity and body fat distribution. Gene expression for these factors was also studied in stromal‐vascular cells (SVCs) and mature adipocytes (MAs) from eight paired fat depots. TRα gene and TRα1 mRNA expression were increased 1.46‐fold (P = 0.006) and 1.80‐fold (P < 0.0001), respectively, in subcutaneous (SC) vs. visceral fat. These differences in gene expression levels were most significant in the obese group, in which the TRα1:TRα2 ratio was 2.24‐fold (P < 0.0001) higher in SC vs. visceral fat. S14 gene expression was also increased by 2.42‐fold (P < 0.0001) and correlated significantly with TRα and TRα1 gene expression and with the TRα1:TRα2 ratio. In agreement with these findings, hnRNP A1:SF2 ratio was decreased by 1.39‐fold (P = 0.001). TRα and S14 levels were 2.1‐fold (P < 0.0001) and 112.4‐fold (P < 0.0001), respectively, higher in MAs than in SVCs from both fat depots. In summary, genes for TR‐α, their upstream regulators, and downstream effectors were differentially expressed in SC vs. omental (OM) adipose tissue. Our findings suggest that TRα1 could contribute to SC adipose tissue expandability in obese subjects.     

Influence of Visceral Obesity and Liver Fat on Vascular Structure and Function in Obese Subjects

Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = ?0.577, P < 0.0001 and r = ?0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r² = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r² = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.     

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.     

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.     

High Expression of Complement Components in Omental Adipose Tissue in Obese Men

Objective: Accumulation of visceral fat is recognized as a predictor of obesity‐related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. Research Methods and Procedures: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real‐time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. Results: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue (～2‐, 4‐, 17‐, 10‐, and 7‐fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). Discussion: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra‐abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.     

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.     

The Associations of LPIN1 Gene Expression in Adipose Tissue With Metabolic Phenotypes in the Chinese Population

The LPIN1 gene, encoding lipin‐1 protein, plays critical roles in adipocyte differentiation and lipid metabolism. This study aimed to analyze the association of LPIN1 mRNA levels in human adipose tissue with metabolic phenotypes. We also examined the association of LPIN1 genetic variation with type 2 diabetes and related metabolic phenotypes in the Chinese population. The relative LPIN1 mRNA levels were measured in abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) obtained from 102 nondiabetic Chinese females. Seven single‐nucleotide polymorphisms (SNPs) spanning from the 5′‐upstream region to the 3′‐end of the LPIN1 gene were genotyped in 1,520 Chinese (760 type 2 diabetic cases and 760 controls). LPIN1 mRNA levels in VAT were negatively correlated with BMI (r = ?0.21, P = 0.03), body fat percentage (r = ?0.22, P = 0.02), plasma triglycerides levels (r = ?0.21, P = 0.03), and plasma leptin levels (r = ?0.63, P = 0.0002). LPIN1 mRNA levels were positively correlated with PPARG and ADIPOQ mRNA levels in both VAT and SAT. No single SNP of the LPIN1 gene was associated with type 2 diabetes in our population. One rare haplotype showed a significant association with type 2 diabetes (odds ratio (OR), 4.35; 95% confidence interval, 1.86–11.75; P = 4 × 10^?4). No SNP or haplotype of the LPIN1 gene was associated with quantitative metabolic traits in the nondiabetic subjects. The results confirmed the association of LPIN1 gene expression in adipose tissue with lower adiposity and favorable metabolic profiles in the Chinese population. However, the LPIN1 gene seemed not to be a major susceptibility gene for type 2 diabetes or related metabolic phenotypes in the Chinese population.     

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.     

Islet-1: a potentially important role for an islet cell gene in visceral fat

Objective: To examine differences in gene expression between visceral (VF) and subcutaneous fat (SF) to identity genes of potential importance in regulation of VF. Methods and Procedures: We compared gene expression (by DNA array and quantitative PCR (qPCR)) in paired VF and SF adipose biopsies from 36 subjects (age 54 ± 15 years, 15 men/21 women) with varying degrees of adiposity and insulin resistance, in chow and fat fed mice (± rosiglitazone treatment) and in c‐Cbl^?/? mice. Gene expression was also examined in 3T3‐L1 preadipocytes during differentiation. Results: A twofold difference or more was found between VF and SF in 1,343 probe sets, especially for genes related to development, cell differentiation, signal transduction, and receptor activity. Islet‐1 (ISL1), a LIM‐homeobox gene with important developmental and regulatory function in islet, neural, and cardiac tissue, not previously recognized in adipose tissue was virtually absent in SF but substantially expressed in VF. ISL1 expression correlated negatively with BMI (r = ?0.37, P = 0.03), abdominal fat (by dual energy X‐ray absorptiometry, r = ?0.44, P = 0.02), and positively with circulating adiponectin (r = 0.33, P = 0.04). In diet‐induced obese mice, expression was reduced in the presence or absence of rosiglitazone. Correspondingly, expression was increased in the c‐Cbl^?/? mouse, which is lean and insulin sensitive (IS). ISL1 expression was increased sevenfold in 3T3‐L1 preadipocytes during early (day 1) differentiation and was reduced by day 2 differentiation. Discussion: An important developmental and regulatory gene ISL1 is uniquely expressed in VF, probably in the preadipocyte. Our data suggest that ISL1 may be regulated by adiposity and its role in metabolic regulation merits further study.     

Assessment of Atrial Electromechanical Delay by Tissue Doppler Echocardiography in Obese Subjects

Our aim was to evaluate whether atrial electromechanical delay measured by tissue Doppler imaging (TDI), which is an early predictor of atrial fibrillation (AF) development, is prolonged in obese subjects. A total of 40 obese and 40 normal‐weight subjects with normal coronary angiograms were included in this study. P‐wave dispersion (PWD) was calculated on the 12‐lead electrocardiogram (ECG). Systolic and diastolic left ventricular (LV) functions, inter‐ and intra‐atrial electromechanical delay were measured by TDI and conventional echocardiography. Inter‐ and intra‐atrial electromechanical delay were significantly longer in the obese subjects compared with the controls (44.08 ± 10.06 vs. 19.35 ± 5.94 ms and 23.63 ± 6.41 vs. 5.13 ± 2.67 ms, P < 0.0001 for both, respectively). PWD was higher in obese subjects (53.40 ± 5.49 vs. 35.95 ± 5.93 ms, P < 0.0001). Left atrial (LA) diameter, LA volume index and LV diastolic parameters were significantly different between the groups. Interatrial electromechanical delay was correlated with PWD (r = 0.409, P = 0.009), high‐sensitivity C‐reactive protein (hsCRP) levels (r = 0.588, P < 0.0001). Interatrial electromechanical delay was positively correlated with LA diameter, LA volume index, and LV diastolic function parameters consisting of mitral early wave (E) deceleration time (DT) and isovolumetric relaxation time (IVRT; r = 0.323, P = 0.042; r = 0.387, P = 0.014; r = 0.339, P = 0.033; r = 0.325, P = 0.041; respectively) and, negatively correlated with mitral early (E) to late (A) wave ratio (E/A) (r = ?0.380, P = 0.016) and myocardial early‐to‐late diastolic wave ratio (E_m/A_m) (r = ?0.326, P = 0.040). This study showed that atrial electromechanical delay is prolonged in obese subjects. Prolonged atrial electromechanical delay is due to provoked low‐grade inflammation as well as LA enlargement and early LV diastolic dysfunction in obese subjects.     

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.     

Retinol‐binding Protein 4 (RBP4) Protein Expression Is Increased in Omental Adipose Tissue of Severely Obese Patients

Visceral fat has been linked to insulin resistance and type 2 diabetes mellitus (T2DM); and emerging data links RBP4 gene expression in adipose tissue with insulin resistance. In this study, we examined RBP4 protein expression in omental adipose tissue obtained from 24 severely obese patients undergoing bariatric surgery, and 10 lean controls (4 males/6 females, BMI = 23.2 ± 1.5 kg/m²) undergoing elective abdominal surgeries. Twelve of the obese patients had T2DM (2 males/10 females, BMI: 44.7 ± 1.5 kg/m²) and 12 had normal glucose tolerance (NGT: 4 males/8 females, BMI: 47.6 ± 1.9 kg/m²). Adipose RBP4, glucose transport protein‐4 (GLUT4), and p85 protein expression were determined by western blot. Blood samples from the bariatric patients were analyzed for serum RBP4, total cholesterol, triglycerides, and glucose. Adipose RBP4 protein expression (NGT: 11.0 ± 0.6; T2DM: 11.8 ± 0.7; lean: 8.7 ± 0.8 arbitrary units) was significantly increased in both NGT (P = 0.03) and T2DM (P = 0.005), compared to lean controls. GLUT4 protein was decreased in both NGT (P = 0.02) and T2DM (P = 0.03), and p85 expression was increased in T2DM subjects, compared to NGT (P = 0.03) and lean controls (P = 0.003). Regression analysis showed a strong correlation between adipose RBP4 protein and BMI for all subjects, as well as between adipose RBP4 and fasting glucose levels in T2DM subjects (r = 0.76, P = 0.004). Further, in T2DM, serum RBP4 was correlated with p85 expression (r = 0.68, P = 0.01), and adipose RBP4 protein trended toward an association with p85 protein (r = 0.55, P = 0.06). These data suggest that RBP4 may regulate adiposity, and p85 expression in obese‐T2DM, thus providing a link to impaired insulin signaling and diabetes in severely obese patients.     

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.     

Depot-specific regulation of autotaxin with obesity in human adipose tissue

Autotaxin (ATX) is a lysophospholipase D involved in synthesis of a bioactive mediator: lysophosphatidic. ATX is abundantly produced by adipocytes and exerts a negative action on adipose tissue expansion. In both mice and humans, ATX expression increases with obesity in association with insulin resistance. In the present study, fat depot-specific regulation of ATX was explored in human. ATX mRNA expression was quantified in visceral and subcutaneous adipose tissue in obese (BMI?>?40?kg/m²; n?=?27) and non-obese patients (BMI?<?25?kg/m²; n?=?10). Whatever the weight status of the patients is, ATX expression was always higher (1.3- to 6-fold) in subcutaneous than in visceral fat. Nevertheless, visceral fat ATX was significantly higher (42?%) in obese than in non-obese patients, whereas subcutaneous fat ATX remained unchanged. In obese patients, visceral fat ATX expression was positively correlated with diastolic arterial blood pressure (r?=?0.67; P?=?0.001). This correlation was not observed with subcutaneous fat ATX. Visceral fat ATX was mainly correlated with leptin (r?=?0.60; P?=?0.001), inducible nitric oxide synthase (r?=?0.58; P?=?0,007), and apelin receptor (r?=?0.50; P?=?0.007). These correlations were not observed with subcutaneous fat ATX. These results reveal that obesity-associated upregulation of human adipose tissue ATX is specific to the visceral fat depot.     

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.