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Introduction: Adipose tissue is considered an important metabolic tissue, in charge of energy storage as well as being able to act in systemic homeostasis and inflammation. Epigenetics involves a series of factors that are important for gene regulation or for chromatin structure, mostly DNA methylation and histone-tail modifications, which can be modified by environmental conditions (nutrition, lifestyle, smoking…). Since metabolic diseases like obesity and diabetes are closely related to lifestyle and nutrition, epigenetic deregulation could play an important role in the onset of these diseases and vice versa. However, little is known about histone marks in human adipose tissue. In a previous work, we developed a protocol for chromatin immunoprecipitation (ChIP) of frozen human adipose tissue. By using this method, this study investigates, for the first time, the H3K4 trimethylation (H3K4me3) mark (open chromatin) on the promoter of several factors involved in adipogenesis, lipid metabolism and inflammation in visceral adipose tissue (VAT) from human subjects with different degrees of body mass index (BMI) and metabolic disease., Methodology: VAT was collected and frozen at -80°C. 100 mg VAT samples were fixed in 0.5% formaldehyde and homogenized. After sonication, the sheared chromatin was immune-precipitated with an anti-H3K4me3 antibody linked to magnetic beads and purified. H3K4me3 enrichment was analyzed by qPCR for LEP, LPL, SREBF2, SCD1, PPARG, IL6, TNF and E2F1 promoters. mRNA extraction on the same samples was performed to quantify gene expression of these genes., Results: H3K4me3 was enriched at the promoter of E2F1, LPL, SREBF2, SCD1, PPARG and IL6 in lean normoglycemic compared to morbid obese subjects with prediabetes. Accordingly H3K4me3 mark enrichment at E2F1, LPL, SREBF2, SCD1, PPARG and IL6 promoters was positively correlated with the BMI and the HOMA-IR. Regression analysis showed a strong relationship between the BMI with H3K4me3 at the promoter of E2F1 and LPL, and with mRNA levels of LEP and SCD. In the case of HOMA-IR, the regression analysis showed associations with H3K4me3 enrichment at the promoter of SCD1 and IL6, and with the mRNA of LEP and SCD1. Moreover H3K4me3 at the E2F1 promoter was positively associated to E2F1 mRNA levels., Conclusions: H3K4me3 enrichment in the promoter of LEP, LPL, SREBF2, SCD1, PPARG, IL6, TNF and E2F1 is directly associated with increasing BMI and metabolic deterioration. The H3k4me3 mark could be regulating E3F1 mRNA levels in adipose tissue, while no associations between the promoter enrichment of this mark and mRNA levels existed for the other genes studied., Competing Interests: The authors have declared that no competing interests exist.

Background: The nuclear protein high-mobility group box 1 (HMGB1) can be passively released by necrotic cells or secreted actively by several cell types to regulate immune and inflammatory responses, as well as tissue remodeling. We herein aimed to characterize the effect of insulin resistance on HMGB1 in adipose tissue and to examine its potential role as a metabolic regulator in β-pancreatic cells., Design: Plasma HMGB1 concentration and adipose HMGB1 expression were assessed in relation to obesity and insulin resistance. Cultured adipocytes from lean and obese patients were used to investigate the intracellular distribution and factors regulating HMGB1 release, as well as to test its effects on adipogenesis and lipid metabolism. A regulatory role for HMGB1 in insulin secretion was also investigated., Results: Circulating HMGB1 was positively associated with body mass index, while adipose HMGB1 mRNA levels correlated with the expression of inflammatory markers. Insulin resistance modified the intracellular distribution of HMGB1 in human adipocytes, with HMGB1 being predominantly nuclear in lean and obese normoglycemic individuals while localized to the cytosol in obese patients with type 2 diabetes. Adipocytes from lean individuals exposed to conditioned media from lipopolysaccharide-stimulated macrophages induced HMGB1 redistribution to the cytoplasm and release. HMGB1 treatment had no effect on differentiation and lipid metabolism in adipocytes. However, HMGB1, whose circulating levels correlated with postload insulin concentration, increased both insulin release and intracellular Ca(2+) concentration in INS-1 cells., Conclusions: These findings show, for the first time, that HMGB1 expression and release by human adipocytes is altered by inflammatory conditions as those imposed by obesity and insulin resistance. Our data reveal a novel role for HMGB1 as a stimulatory factor of insulin secretion of β-pancreatic cells.

Objective: The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans., Methods: p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated., Results: Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes., Conclusion: Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces.

The role of the gut microbiota in the induction of metabolic diseases has now been increasingly recognized worldwide. Indeed, a specific gut microbiota has been shown to characterize lean versus obese phenotypes both in humans and mice. We have also recently demonstrated that a precise gut microbiota is associated with the host's responsiveness to a high-fat diet. Therefore, we hypothesized that insulin resistance in humans could also be linked to a specific gut microbiota. To this aim, microbial DNA and RNA were extracted from the appendix contents of insulin-resistant versus insulin-sensitive obese subjects, matched for body mass index and age, and analyzed by DNA- and RNA-DGGE. Microbial DNA analysis showed that the patients fully segregated according to their degree of insulin action. Conversely, microbial RNA investigation showed that some degree of homology still existed between insulin-sensitive and insulin-resistant patients. Quantitative trait analysis, ordinary least squares regression, principal components regression, partial least squares, canonical correlation analysis, and canonical correspondence analysis also showed a net separation of the two phenotypes analyzed. We conclude that a specific gut microbial profile is associated with insulin action in humans.

Context: Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice., Objective: The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes., Design, Patients, and Main Outcome Measure: Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed., Results: In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels., Conclusions: Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.

Background: Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitus and cardiovascular complications. Bariatric surgery is the most effective strategy for treating morbidly obese patients. We evaluated the metabolic changes that occur in the early stage after 2 types of bariatric surgery, biliopancreatic diversion of Scopinaro (BPD) and sleeve gastrectomy (SG), in morbidly obese patients., Methods: The study was undertaken in 31 nondiabetic morbidly obese patients (7 men and 24 women). Of the 31 patients, 18 underwent BPD and 13 underwent SG. All patients were examined before bariatric surgery (baseline) and at 15, 30, 45, and 90 days postoperatively., Results: Significant improvement occurred in the anthropometric variables after the 2 types of bariatric surgery, without significant differences between the 2 types of interventions. In patients undergoing BPD, the serum glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, and free fatty acids were significantly reduced. The changes that occurred in these biochemical variables after SG were not significant. Insulin resistance decreased significantly during the 90 days after surgery, with the greatest decrease at 15 days. However, in the patients who underwent SG, insulin resistance worsened at 15 days and later diminished., Conclusion: The results of the present study have shown that the surgical technique that excludes the duodenum (i.e., BPD) has immediate postoperative changes in the degree of insulin resistance in morbidly obese patients compared to those techniques that do not exclude the duodenum (i.e., SG)., (Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

Background: The storage capacity of adipose tissue may be an important factor linking obesity, insulin resistance (IR), and associated morbidities. The aim of this study was to analyze the expression of lipogenic and lipolytic genes in adipose tissue and the influence of IR., Methods: We studied the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) and lipogenic and lipolytic enzymes in the visceral (VAT) and subcutaneous adipose tissue (SAT) from 23 morbidly obese patients (MO; 13 with low IR and ten with high IR) and from 15 healthy, lean controls., Results: In the VAT and SAT from the MO, we found an increased expression of PPARγ (p = 0.001 and p = 0.022, respectively), acyl-coenzyme A (CoA)/cholesterol acyltransferase (p < 0.001 and p < 0.001), aquaporin 7 (p < 0.001 and p = 0.003), and adipose triglyceride lipase (p < 0.001 and p < 0.001) and a reduced expression of acetyl-coenzyme A carboxylase (p = 0.004 and p < 0.001), independently of the state of IR. The expression of phosphoenolpyruvate carboxykinase and acyl-CoA synthetase, however, was significantly lower in the MO with high IR (p < 0.05). Glycerol kinase (p = 0.010), hormone-sensitive lipase (p < 0.001), and perilipin (p = 0.006) were only significantly increased in VAT. Acyl-CoA synthetase (p = 0.012) and fatty acid binding protein-4 (p = 0.003) were only significantly decreased in SAT. The expression of the genes studied was only greater in the SAT than the VAT in the controls., Conclusion: Our results show an upregulation of genes facilitating triglyceride/fatty acid cycling and a reduction in the genes involved in de novo synthesis of fatty acids in morbid obesity. The expression of some of the genes studied seems to be related with the state of IR. VAT and SAT differ metabolically and also between controls and MO.

Objective: Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations., Design: We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants)., Results: Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes., Conclusion: Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

Background: Many studies have focused on the physiological parameters and genetic predisposition of subjects presenting both obesity and insulin resistance (IR) and it has been suggested that the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) Pro12Ala variant may contribute to the observed variability in insulin sensitivity. We investigated whether the PPARgamma2 mRNA expression levels are associated with IR in morbid obesity in adipose and muscle tissues., Materials and Methods: In this study, tissue biopsies were obtained from 26 morbidly obese (MO) patients and eight controls. The MO patients were divided into two groups: those with a low homeostasis model assessment of IR (HOMA-IR < 5) (MO-nonIR) and those with a high HOMA-IR (HOMA-IR > or = 8) (MO-IR). PPARgamma1, PPARgamma2 and aP2 mRNA expression levels were measured using quantitative RT-PCR., Results: The study found that PPARgamma2 mRNA expression in visceral adipose tissue (VAT) was significantly lower in the MO patients (P = 0.002) than the controls. Moreover, the PPARgamma2 mRNA expression was lower in VAT (P < 0.05) and muscle tissue (P < 0.01), and higher in subcutaneous adipose tissue (SAT) (P < 0.01) in the MO-IR than the MO-nonIR group. By contrast, PPARgamma1 mRNA expression levels were not dependent on IR. Finally, the MO patients showed a significant negative correlation between PPARgamma2 mRNA expression and IR (r = -0.396, P = 0.020) in VAT and a positive correlation in SAT (r = 0.826, P < 0.001). The variable that best explained the IR was PPARgamma2 mRNA expression in SAT (P = 0.002)., Conclusions: These data show that PPARgamma2 mRNA is expressed differently in the two types of MO patients and is associated with IR.

Hyperuricaemia is one of the components of metabolic syndrome. Both oxidative stress and hyperinsulinism are important variables in the genesis of this syndrome and have a close association with uric acid (UA). We evaluated the effect of an oral glucose challenge on UA concentrations. The study included 656 persons aged 18 to 65 years. Glycaemia, insulin, UA and plasma proteins were measured at baseline and 120 min after an oral glucose tolerance test (OGTT). The baseline sample also included measurements of total cholesterol, triacylglycerol (TAG) and HDL-cholesterol. Insulin resistance was calculated with the homeostasis model assessment. UA levels were significantly lower after the OGTT (281.93 (sd 92.19) v. 267.48 (sd 90.40) micromol/l; P < 0.0001). Subjects with a drop in UA concentrations >40.86 micromol/l (>75th percentile) had higher plasma TAG levels (P = 0.0001), baseline insulin (P = 0.02) and greater insulin resistance (P = 0.034). Women with a difference in plasma concentrations of UA above the 75th percentile had higher baseline insulin levels (P = 0.019), concentration of plasma TAG (P = 0.0001) and a greater insulin resistance index (P = 0.029), whereas the only significant difference in men was the level of TAG. Multiple regression analysis showed that the basal TAG levels, insulin at 120 min, glycaemia at 120 min and waist:hip ratio significantly predicted the variance in the UA difference (r2 0.077). Levels of UA were significantly lower after the OGTT and the individuals with the greatest decrease in UA levels are those who have greater insulin resistance and higher TAG levels.

Objective: Few epidemiological studies have examined the relationship of dietary fatty acids, especially MUFA, with the interrelation between insulin secretion and insulin resistance. We assessed the relation of dietary fatty acids with insulin secretion in a free-living population., Design and Setting: This cross-sectional, population-based study was undertaken in Pizarra, a small town in Spain., Subjects and Methods: Anthropometrical data were collected for 1226 persons selected randomly from the municipal census, 538 of whom (randomly chosen) were given a prospective, quantitative, 7-day nutritional questionnaire. The fatty acid composition of the serum phospholipids was used as a biological marker of the type of fat consumed. Beta-cell function (betaCFI) and insulin-resistance index (IRI) were estimated by the Homeostasis Model Assessment., Results: To determine which factors influence the variability of the betaCFI, we analyzed the variance of the betaCFI according to sex, the presence of carbohydrate metabolism disorders and the different components of the diet, adjusting the models for age, body mass index (BMI) and IRI. The dietary MUFA and polyunsaturated fatty acids (PUFA) contributed to the variability of the betaCFI, whereas only the proportion of serum phospholipid MUFA, but neither the saturated fatty acids nor the PUFA accounted for part of the variability of the betaCFI in a multiple regression analysis., Conclusion: The results of this population-based study corroborate the results of other clinical and experimental studies suggesting a favorable relationship of MUFA with beta-cell insulin secretion., Sponsorship: Fondo de Investigación Sanitaria, Junta de Andalucía and the Asociación Maimónides.

Activation of the PPAR gamma 2 gene (PPARG2) improves the action of insulin and its lipid metabolism. We examined the association between Pro12Ala polymorphism of PPARG2, type 2 diabetes mellitus (DM2), and peripheral insulin sensitivity in a population with a high intake of oleic acid. A cross-sectional, population-based study was undertaken in Pizarra, a small town in the province of Malaga in southern Spain. A total of 538 subjects, aged 18-65 y, were selected randomly from the municipal census. All subjects underwent a clinical, anthropometrical, and biochemical evaluation, including an oral glucose tolerance test and Pro12Ala polymorphism of PPARG2. Insulin resistance was measured by homeostasis model assessment. Those subjects with the Ala-12 allele had an odds ratio for impaired fasting glucose of 0.55, for impaired glucose tolerance of 0.59, and for DM2 of 0.30. The intake of monounsaturated fatty acids (MUFA) contributed to the variance of the homeostasis model assessment insulin resistance index (HOMA IR) (P = 0.04), with a 2-way interaction between the Ala-12 allele of PPARG2 and the intake of MUFA (P = 0.005). The results suggest the existence of an interaction between Pro12Ala polymorphism of PPARG2 and dietary MUFA, such that obese people with the Ala-12 allele have higher HOMA IR values, especially if their intake of MUFA is low.

The aim of this study was to evaluate patterns of insulin resistance in the general population. The study was cross sectional. Clinical, anthropometric, and lipid measurements were made in 1226 persons aged 18-65 years. An oral glucose tolerance test (OGTT) was performed in 1020 subjects, with insulin levels determined at baseline and after 2 h. The homeostasis model assessment insulin resistance index (HOMA IR) and HOMA beta-cell function were calculated. Compared with subjects with normal glucose tolerance, the groups with abnormal OGTT had different baseline insulinemia, 2 h post OGTT insulinemia, HOMA IR and HOMA beta-cell indices. Serum insulin levels at baseline and 2 h after OGTT showed a characteristic pattern for each category of glucose tolerance, resulting from the different insulin responses. In the subjects with normal glucose tolerance, the pattern of the relationships between both types of serum insulin levels was exactly the same, so that it was possible to determine risk groups according to the ratio of baseline serum insulin/2 h insulin. HOMA IR and HOMA beta-cell were significantly associated with the risk of impaired fasting glucose, previously unknown diabetes mellitus, and known diabetes mellitus. These results support the rationale for introducing preventive measures against insulin resistance in the general population.

Aim: To evaluate the relation between type of dietary fatty acid and degree of insulin resistance., Design: A cross-sectional study., Methods: Anthropometrical data were measured in 538 subjects, aged 18-65 Years, selected randomly from the municipal census of Pizarra (Spain). An oral glucose tolerance test (OGTT) was given to all subjects and measurements were made of glycemia, insulinemia and the proportion of fatty acids in plasma phospholipids. Insulin resistance (IR) was estimated by homeostasis model assessment. Samples of cooking oil being used were obtained from the kitchens. The strength of association between variables was measured by calculating the odds ratio (OR) from logistic models, and the relationships were measured by linear correlation coefficients., Results: Insulin resistance was significantly less in people who used olive oil compared with those who used sunflower oil or a mixture. Statistical significance remained in the group of people with normal OGTT after adjusting for obesity. In the whole sample, IR correlated negatively with the concentration of oleic acid (r=-0.11; P=0.02) and positively with that of linoleic acid (r=0.10; P=0.02) from the cooking oil. In subjects with normal OGTT, IR correlated negatively with oleic acid from cooking oil (r=-0.17; P=0.004) and from plasma phospholipids (r=-0.11; P=0.01) and positively with the concentration of linoleic acid in cooking oil (r=0.18; P=0.004) and plasma phospholipids (r=0.12; P=0.005). The risk (OR) of having raised IR was significantly lower in people who consumed olive oil, either alone (OR=0.50) or mixed (OR=0.52) compared with those who consumed only sunflower oil., Conclusion: There is an association between the intake of oleic acid, the composition of oleic acid in plasma phospholipids and peripheral insulin action.

Background:Surfactant protein-D (SFTPD) is a component of the lung innate immunity that enhances clearance of pathogens and modulates inflammatory responses. An inverse association of putative, lung-derived circulating SFTPD with obesity has been reported but no information is available concerning possible SFTPD gene expression in human adipose tissue.Methods:SFTPD gene expression was analyzed in human omental (OM; n=156) and subcutaneous (SC; n=106) adipose tissue, and in isolated fat cells (n=12) in association with measures of obesity and glucose tolerance.Results:SFTPD gene was expressed in human adipose tissue and adipocytes. This expression was decreased in OM and SC adipose tissue from obese subjects with (−47%, P<0.0001; and −37%, P=0.048) and without (−34%, P=0.001; and −22%, P=0.08; respectively) type 2 diabetes when compared with the control group. Indeed, OM SFTPD was inversely associated with body mass index (r=−0.33, P<0.0001), percent fat mass (r=−0.36, P<0.0001), waist perimeter (r=−0.26, P=0.002), diastolic blood pressure (r=−0.21, P=0.018) and fasting glucose (r=−0.21, P=0.012); and positively linked to the expression of insulin receptor substrate 1 (IRS1; r=0.25, P=0.004), perilipin A (PLIN; r=0.38, P=0.007) and fatty acid synthase (FASN; r=0.36, P<0.0001). Accordingly, increased SFTPD (4.5-fold, P=0.02) was detected in isolated adipocytes when compared with the stromal-vascular cell fraction, in parallel to IRS1, FASN and PLIN.Conclusions:Both OM and SC adipose tissue (mainly mature adipocytes) express SFTPD. This expression decreases with obesity and impaired glucose tolerance. [ABSTRACT FROM AUTHOR]

Objectives Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein ( ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. Methods Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay ( ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. Results HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls ( P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol ( HDLc) in men ( B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol ( r = 0.312; P < 0.001) and HDLc ( r = 0.216; P = 0.005). Conclusions HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc. [ABSTRACT FROM AUTHOR]