OLETF大鼠脂肪组织chemerin及其受体1的基因表达

用实时定量PCR检测OLETF大鼠脂肪组织中chemerin及其受体1 mRNA的表达,结果两者表达水平较对照组明显升高(P<0.05或P<0.01),且网膜脂肪组织高于皮下脂肪组织(P<0.05或P<0.01),说明脂肪因子chemerin及其受体1基因表达的变化可能是肥胖、胰岛素抵抗和2型糖尿病发病的机制之一.     

Chemerin is a novel adipokine associated with obesity and metabolic syndrome

Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.     

Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity

Chemerin is a chemoattractant adipokine that regulates adipogenesis and may induce insulin resistance. Chemerin serum concentrations are elevated in obese, insulin-resistant, and inflammatory states in vivo. Here we investigate the role of omental (OM) and subcutaneous (SC) adipose tissue chemerin and CMKLR1 messenger RNA (mRNA) expression in human obesity. In addition, we test the hypothesis that changes in chemerin serum concentrations are primarily associated with reduced body fat mass in the context of 3 weight loss intervention studies. Chemerin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which OM and SC chemerin mRNA expression has been analyzed as well as in 3 interventions including 12 weeks of exercise (n = 60), 6 months of calorie-restricted diet (n = 19) studies, and 12 months after bariatric surgery (n = 32). Chemerin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes mellitus and correlates with circulating chemerin, body mass index (BMI), percentage body fat, C-reactive protein, homeostasis model assessment of insulin resistance, and glucose infusion rate in euglycemic-hyperinsulinemic clamps. CMKLR1 mRNA expression was not significantly different between the 2 fat depots. Obesity surgery-induced weight loss causes a significant reduction on both OM and SC chemerin expression. All interventions led to significantly reduced chemerin serum concentrations. Decreased chemerin serum concentrations significantly correlate with improved glucose infusion rate and reduced C-reactive protein levels independently of changes in BMI. Insulin resistance and inflammation are BMI-independent predictors of elevated chemerin serum concentrations. Reduced chemerin expression and serum concentration may contribute to improved insulin sensitivity and subclinical inflammation beyond significant weight loss.     

Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance

IntroductionObesity is strongly related to type-2 diabetes (T2DM), but there is a subset of obese individuals that remains relatively insulin sensitive and metabolically healthy. This study determined to what extent differences in metabolic health in obese women are associated with differences in adipose tissue and/or systemic inflammation.MethodsThe subject group consisted of age comparable lean (n = 12) and obese women either with T2DM (n = 28) or normal glucose tolerance (NGT; n = 26). Number of crown like structures (CLS) and adipocyte size were measured in subcutaneous and visceral adipose tissue of the obese women. Circulating cytokine and free fatty acid (FFA) levels, as well as number and activation status of peripheral leukocytes were determined.ResultsObese T2DM subjects showed higher circulating levels of IL-6, FFA and glycerol as compared to obese NGT subjects. Obese T2DM subjects had higher absolute numbers of peripheral leukocytes which were mainly due to an increase of T helper cells. Activation status of circulating cytotoxic T (CD8+CD25 +) and B (CD19+CD38 +) cells was significantly increased in obese NGT subjects as compared to lean but was not different between the two obese groups. Subcutaneous adipose tissue of obese T2DM subjects contained more CLS than adipose tissue of obese NGT subjects.ConclusionObese T2DM subjects show higher FFA levels and adipose tissue macrophage infiltration in addition to higher levels of circulating IL-6 and numbers of CD4 + T cells than obese NGT subjects. Hence, obese T2DM subjects show a higher extent of inflammation at both the systemic and adipose tissue level.     

Relationship between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha gene expression in obese human adipose tissue

OBJECTIVE: To investigate in human adipose tissue a possible relationship between per oxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid receptor alpha (RARalpha) gene expression, two genes involved in the control of adipocyte differentiation. SUBJECTS: Ten lean control women (age 31-60 y, body mass index (BMI) 18-24.7 kg/m(2)) and an obese group of 15 women (age 27-62 y, BMI 30-57.5 kg/m(2)), of whom 10 subjects were in weight-gain phase and five were in weight-loss phase. MEASUREMENTS: We assessed the relative PPARgamma and RARalpha mRNA levels in subcutaneous abdominal adipose tissue using a real-time PCR method. RESULTS: PPARgamma mRNA level were significantly increased (+91%; P<0.01) in obese women compared to lean control women. In the obese group, we observed a PPARgamma mRNA level 42% lower in weight-loss obese than in weight-gain obese subjects. We obtained a positive correlation (r=0.56; P<0.01) between PPARgamma mRNA level and the BMI of all subjects. Relative mRNA abundance level of RARalpha in subcutaneous adipose tissue of obese subjects is significantly lower than in control subjects (-56%, P<0.01), and a negative correlation was found between PPARgamma and RARalpha mRNA levels in subcutaneous adipose tissue of subjects study (r=-0.75; P<0.01). CONCLUSION: Our findings suggest that obesity is associated with an inverse relationship between PPARgamma and RARalpha expressions in human subcutaneous adipose tissue. Modulations of nuclear receptor profile could be an important event in the body's early adaptive mechanisms promoting adipose tissue plasticity and leading to the onset of obesity.     

TCF7L2 gene expression in human visceral and subcutaneous adipose tissue is differentially regulated but not associated with type 2 diabetes mellitus

Variants in the TCF7L2 gene have been associated with type 2 diabetes mellitus (T2DM), but the causal variant(s) is still unknown. We studied the TCF7L2 messenger RNA (mRNA) expression in paired samples of visceral and subcutaneous adipose tissue from 49 subjects using quantitative real-time polymerase chain reaction and its relation to obesity and T2DM. All subjects were genotyped for the previously described TCF7L2 diabetes risk variants. Independent of age, sex, obesity, and diabetes status, we found >3-fold higher TCF7L2 mRNA expression in subcutaneous compared with visceral adipose tissue. There was no correlation between visceral and subcutaneous TCF7L2 expression. No differences in adipose tissue TCF7L2 mRNA expression levels were found between diabetic and nondiabetic subjects, or between lean and obese subjects (all Ps > .05). In addition, there was no association between TCF7L2 genetic variants and mRNA expression. Based on our data, TCF7L2 mRNA expression is fat-depot specific but does not seem to provide the mechanistic link explaining genetic association with T2DM.     

Benefit of insufficient gestational weight gain in obese women with gestational diabetes mellitus: A multicenter study in Portugal

BackgroundBoth obesity and gestational diabetes mellitus (GDM) are independent risk factors for adverse maternal and fetal outcomes. The Institute of Medicine (IOM) recommends different targets for an adequate gestational weight gain (GWG), depending on the prepregnancy body mass index, but they have been questioned. We aim to compare obese pregnant women with GDM according to GWG stratification (insufficient, adequate and excessive) with regard to maternal and neonatal outcomes and to clarify whether insufficient GWG can be associated with better outcomes.MethodsA multicenter observational study with prospectively collected data of obese singleton pregnant women with GDM was conducted. GWG was expressed according to the 2009 IOM’s recommendations.ResultsOf 4563 obese women with GDM, 34.5%, 30.4% and 35.2% registered insufficient, adequate and excessive GWG, respectively. Multiple logistic regression analysis revealed that women with insufficient GWG had lower odds of gestational hypertension, preeclampsia, caesarean section, large for gestational age (LGA) neonates and prediabetes in postpartum. Despite the higher incidence of small for gestational age (SGA) neonates, they were not associated with adverse outcomes. Women with excessive GWG had higher odds of caesarean section, macrosomic and LGA neonates.ConclusionsInsufficient GWG in obese women with GDM was beneficial due to better maternal and neonatal outcomes. In clinical practice, we should be strict with regard to weight gain in obese pregnant women with GDM and encourage a reduced GWG, provided an adequate fetal growth is guaranteed.     

Inflammation biomarkers and inflammatory genes expression in metabolically healthy obese patients

Background and aimsObesity without metabolic alterations (Metabolically Healthy Obesity, MHO) is a condition with a risk of death and cardiovascular disease lower than that of obesity associated with metabolic alterations (Metabolically Unhealthy Obesity, MUO) and similar to that of healthy non obese individuals. Inflammation is considered as a key risk factor mediating the adverse health outcomes in obesity.Methods and resultsWe compared circulating levels of thirteen major cytokines and adipokines and the expression profiles of fifteen pro-inflammatory and two anti-inflammatory genes in visceral and subcutaneous adipose tissue in a series of 16 MHO patients and in 32 MUO patients that underwent bariatric surgery. MHO was defined according to the most applied definition in current literature.Serum levels of a large set of major cytokines and adipokines did not differ between MHO and MUO patients (p ≥ 0.15). Analyses of the expression profile of pro-inflammatory and anti-inflammatory genes in subcutaneous and visceral adipose tissue failed to show differences between MHO and MUO patients (p ≥ 0.07). Sensitivity analyses applying two additional definitions of MHO confirmed the results of the primary analysis.ConclusionIn a series of metabolically healthy obese patients neither circulating levels of major cytokines and adipokines nor the gene expression profile of a large set of pro-inflammatory and anti-inflammatory genes in subcutaneous and visceral fat differed from those in metabolically unhealthy obese patients.     

Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women

Insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) expression may provide an indirect reflection of the capacity of adipocytes to respond to insulin stimulation. We examined messenger RNA (mRNA) expression of these genes in omental and subcutaneous adipose tissue of women. Paired omental and subcutaneous adipose tissue samples were obtained from 36 women (age, 47 ± 5 years; body mass index, 28.0 ± 5.4 kg/m²) undergoing gynecologic surgeries. Total adiposity and visceral adiposity were assessed by dual-energy x-ray absorptiometry and computed tomography. The GLUT4 and IRS-1 mRNA expression levels were both significantly higher in subcutaneous compared with omental adipose tissue. A negative correlation was observed between body fat percentage and subcutaneous adipose tissue GLUT4 (r = −0.39, P < .05) and IRS-1 (r = −0.30, P < .08) mRNA abundance. However, in omental fat, only GLUT4 mRNA was inversely associated with body fat percentage (r = −0.53, P < .001). Moreover, the homeostasis model assessment of insulin resistance index was associated with mRNA expression of subcutaneous GLUT4 (r = −0.56, P < .001), subcutaneous IRS-1 (r = −0.51, P < .01), and omental GLUT4 (r = −0.54, P < .001), but not omental IRS-1. Interestingly, plasma adiponectin was only associated with subcutaneous GLUT4 (r = 0.48, P < .01) and IRS-1 (r = 0.48, P < .05) mRNA expression. The GLUT4 protein, unlike mRNA expression, was higher in omental than in subcutaneous adipose tissue. However, abdominal obesity-related differences in protein or mRNA expression were similar. Omental IRS-1 expression was low and unaffected by visceral obesity. In contrast, omental and subcutaneous GLUT4 as well as subcutaneous IRS-1 were reduced in visceral obesity. This divergent pattern of expression may reflect a lower capacity of omental adipose tissue to respond to insulin stimulation at all adiposity levels.     

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors α and β were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-α, CD68, IL-6, IL-8, ERα, ERβ) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.     

巨噬细胞移动抑制因子对妊娠期糖尿病胰岛素抵抗及胰岛β细胞功能的影响

研究巨噬细胞移动抑制因子在妊娠期糖尿病患者血清中的变化及其在脂肪组织中的表达,探讨其对妊娠期糖尿病胰岛素抵抗及胰岛β细胞功能的影响.选择2008年2月至2009年2月在青岛大学医学院附属医院和泰安市中心医院产科门诊及住院孕妇120例,其中GDM组60例,正常糖耐量组(对照组)60例.GDM孕妇血清MIF显著高于正常糖耐量孕妇[(3.58±1.02对1.23±0.62)ng/ml,P<0.01].多元逐步回归分析显示,孕前和孕晚期体重指数是影响血清MIF的独立相关因素(r2=0.516).妊娠期糖尿病患者血清MIF显著升高,其脂肪组织MIF mRNA表达增强;MIF可使胰岛素抵抗程度增加,并影响胰岛B细胞的功能;孕前和孕晚期体重指数是影响血清MIF的独立相关因素.     

Oestrogen receptor alpha gene expression levels are reduced in obese compared to normal weight females

OBJECTIVE: To determine whether oestrogen receptor (ER)alpha messenger RNA (mRNA) levels or single nucleotide polymorphisms (SNPs) are associated with obesity in Swedish women. DESIGN: ERalpha mRNA expression levels were measured by real-time qPCR in subcutaneous adipose tissue from non-obese (N=16, BMI<30) and obese (N=17, BMI>or=30) women. In addition, ERalpha mRNA expression levels were determined in isolated adipocytes. ERalpha promoter usage was characterized by 5' RACE and by real-time qPCR in subcutaneous adipose tissue from the same non-obese and obese women. Two ERalpha SNPs were scored in 509 non-obese and 489 obese females. RESULTS: ERalpha mRNA expression levels were lower in obese compared to non-obese women in both subcutaneous adipose tissue and in adipocytes. We show that two ERalpha promoters are differentially utilized in obese and non-obese individuals. We did not find any significant association between obesity and the ERalpha SNPs or haplotypes assayed. CONCLUSION: The reduced ERalpha mRNA levels observed in adipose tissue from obese compared to non-obese women support a role for oestrogen signaling via ERalpha, in control of body weight. Mechanistic studies of the role of ERalpha in adipocytes and how its expression is regulated in relation to fat mass should be performed. The latter studies should focus on the two promoters that are used differently in obese and non-obese individuals.     

Markers of endothelial cell dysfunction are increased in human omental adipose tissue from women with pre-existing maternal obesity and gestational diabetes

Objective

To determine the effect of maternal obesity and gestational diabetes mellitus (GDM) on the expression and release of genes involved in endothelial cell dysfunction in human placenta and omental adipose tissue.

Materials/Methods

Human placenta and omental adipose tissue were obtained from non-obese and obese normal glucose tolerant (NGT) women and women with GDM at the time of Caesarean section. Quantitative RT-PCR was performed to determine the level of expression. Tissue explants were performed to determine the release of proteins of interest.

Results

There was no effect of pre-existing maternal obesity or GDM on placental gene expression or secretion of members of the VEGF family members (PLGF and VEGF-A expression and secretion; sFlt-1 release; VEGFR1 and VEGFR2 mRNA expression); FGFR1 mRNA expression, FGF2 mRNA expression and secretion; endoglin mRNA expression and secretion (sEng); and the adhesion molecules ICAM-1 and VCAM-1. On the other hand, in omental adipose tissue, pre-existing maternal obesity and GDM were associated with increased gene expression of PLGF, endoglin and ICAM-1 and increased secretion of PLGF, sFlt-1, FGF2, sEng and sICAM-1. There was, however, no effect of maternal pre-existing obesity and GDM on VEGF-A, VEGFR1, VEGFR2, FGFR1 and VCAM-1 expression or secretion.

Conclusions

This study demonstrated the presence of abnormal expression and secretion of angiogenic proteins and adhesion molecules in omental adipose tissue, but not placenta, from pregnant women with GDM and pre-existing maternal obesity. Increased angiogenic and adhesion molecules released from adipose tissue may affect angiogenesis, inflammation and or lipid and glucose metabolism in both mum and her offspring.     

Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity

Objectives:

Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specific characteristics of NAFLD, such as steatosis and inflammation. We aimed to address this question by simultaneously examining the adipokine expression in three tissue types in obese individuals.

Methods:

We enrolled 93 severely obese individuals with NAFLD, varying from simple steatosis to severe non-alcoholic steatohepatitis. Their expression of 48 adipokines in the liver, visceral and subcutaneous adipose tissue (SAT) was correlated to their phenotypic features of NAFLD. We further determined whether the correlations were tissue specific and/or independent of covariates, including age, sex, obesity, insulin resistance and type 2 diabetes (T2D).

Results:

The expression of adipokines showed a liver- and adipose tissue-specific pattern. We identified that the expression of leptin, angiopoietin 2 (ANGPT2) and chemerin in visceral adipose tissue (VAT) was associated with different NAFLD features, including steatosis, ballooning, portal and lobular inflammation. In addition, the expression of tumor necrosis factor (TNF), plasminogen activator inhibitor type 1 (PAI-1), insulin-like growth factor 1 (somatomedin C) (IGF1) and chemokine (C-X-C motif) ligand 10 (CXCL10) in the liver tissue and the expression of interleukin 1 receptor antagonist (IL1RN) in both the liver and SAT were associated with NAFLD features. The correlations between ANGPT2 and CXCL10, and NAFLD features were dependent on insulin resistance and T2D, but for the other genes the correlation with at least one NAFLD feature remained significant after correcting for the covariates.

Conclusions:

Our results suggest that in obese individuals, VAT-derived leptin and chemerin, and hepatic expression of TNF, IGF1, IL1RN and PAI-1 are involved in the development of NAFLD features. Further, functional studies are warranted to establish a causal relationship.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

探讨中国汉族人群血清视黄醇结合蛋白4(RBP4)水平与妊娠糖尿病的关系.收集2005年7月至2007年12月在瑞金医院妇产科行常规产前检查的孕妇195例(妊娠糖尿病组99例,正常糖耐量组96例),同时收集65例非妊娠期健康育龄期妇女作为对照组,所有受试者均排除急慢性疾病,并统一用酶联免疫法检测血清RBP4水平.与非妊娠正常对照组相比,妊娠期妇女血清RBP4水平均明显升高,妊娠糖尿病患者血清RBP4水平较正常妊娠妇女显著升高[(43.04±1.85对33.84±2.17)ms/L,P<0.01].在妊娠期妇女中,多元逐步回归分析显示,胰岛素抵抗指数(HOMA-IR)和甘油三酯是血清RBP4水平升高的独市危险因素(r2=0.165).本研究结果提示,妊娠期妇女血清RBP4水平较非妊娠妇女显著升高,而与正常孕妇相比,妊娠糖尿病患者血清RBP4水平更高;在妊娠期妇女中胰岛素抵抗和甘油三酯水平与RBP4水平显著正相关.     

Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity

Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue. In this context, we here demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous adipose tissue was significantly reduced in obese subjects as compared with nonobese subjects. Adipose tissue AGT mRNA level in obese mice was also lower as compared with their lean littermates; however, the hepatic AGT mRNA level remained unchanged. When 3T3-L1 adipocytes were cultured for a long period, the adipocytes became hypertrophic with a marked increase in the production of reactive oxygen species. Expression and secretion of AGT continued to decrease during the course of adipocyte hypertrophy. Treatment of the 3T3-L1 and primary adipocytes with reactive oxygen species (hydrogen peroxide) or tumor necrosis factor α caused a significant decrease in the expression and secretion of AGT. On the other hand, treatment with the antioxidant N-acetyl cysteine suppressed the decrease in the expression and secretion of AGT in the hypertrophied 3T3-L1 adipocytes. Finally, treatment of obese db/db mice with N-acetyl cysteine augmented the expression of AGT in the adipose tissue, but not in the liver. The present study demonstrates for the first time that oxidative stress dysregulates AGT in obese adipose tissue, providing a novel insight into the adipose tissue-specific interaction between the regulation of AGT and oxidative stress in the pathophysiology of obesity.     

Vitamin D and gestational diabetes: a systematic review and meta-analysis

BackgroundConflicting results currently exists on the association between vitamin D and glucose metabolism. The role of maternal vitamin D status in gestational diabetes mellitus (GDM) is not clear. This meta-analysis aimed to examine this role in women with GDM compared with normal glucose tolerance (NGT).MethodsWe performed a systematic review and meta-analysis by searching MEDLINE database, the Cochrane library and Uptodate® Online for English-language literature up to September 2011. Summary odds ratios were calculated using a random-effects model meta-analysis.ResultsSeven observational studies were eligible for the meta-analysis, including 2146 participants of whom 433 were diagnosed with GDM. Four studies reported a high incidence of vitamin D deficiency in pregnant women (> 50%). Overall vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/l) in pregnancy was significantly related to the incidence of GDM with an odds ratio of 1.61 (95% CI 1.19–2.17; p = 0.002). Serum 25OHD was significant lower in participants with GDM than in those with NGT (? 5.33 nmol/l (95% CI ? 9.73 to ? 0.93; p = 0.018).ConclusionsThis meta-analysis indicates a significant inverse relation of serum 25OHD and the incidence of GDM. However, it remains unclear whether this association is causal due to the observational study design of the studies. Clinical trials are needed to examine whether vitamin D supplementation will improve glycemic control in women with GDM.     

Human subcutaneous adipose tissue Glut 4 mRNA expression in obesity and type 2 diabetes

Cellular resistance to insulin caused by reduced glucose transport and metabolism is a primary defect leading to the development of metabolic disease. While the etiology of insulin resistance is multifactorial, reduced insulin action is associated with impaired activity of the glucose transporter GLUT4 in insulin-sensitive tissues. Yet, the role of adipose tissue GLUT4 deregulation in the pathogenesis of insulin resistance, obesity, and diabetes is still unclear. In this study, we assessed the relative GLUT4 level in human subcutaneous adipose tissue from obese, diabetic, and diabetic obese versus control subjects, using a real-time PCR method. GLUT4 mRNA levels were considerably decreased among type 2 diabetic patients compared with those of the controls (P < 0.01), whereas no such difference was found between obese and normal-weight controls. Multiple linear regressions analysis in both diabetic non-obese and diabetic obese groups showed a negative correlation between GLUT4 mRNA expression and both markers of obesity or insulin resistance (P < 0.01). However, in obese group, GLUT4 was inversely associated only with HOMA-IR (P < 0.01). Our findings showed that adipose GLUT4 gene expression changes were more related to insulin resistance and type 2 diabetes rather than to obesity.