脂联素mRNA在肥胖症患者腹部皮下与网膜脂肪组织中表达水平的研究

目的探讨肥胖症患者腹部皮下脂肪组织与大网膜脂肪组织脂联素的表达水平及与BMI、WHR、血脂、胰岛素敏感性的关系。方法用半定量RT-PCR方法检测19例肥胖症患者(BMI≥25·0kg/m2)和28例非肥胖症患者(BMI<25·0kg/m2)腹部皮下与大网膜脂肪组织脂联素mRNA的表达水平,并测量BMI、WHR、BP,FPG、FIns、血脂和胰岛素抵抗指数(HOMA-IR)。结果(1)肥胖组大网膜脂肪组织脂联素mRNA表达水平显著低于非肥胖组(P<0·05),肥胖组大网膜脂肪组织脂联素mRNA水平显著低于皮下脂肪组织(P<0·05)。(2)肥胖组FIns、HOMA-IR、BP、TG与VLDL-C均高于非肥胖组(P<0·05~P<0·01)。(3)非肥胖组中网膜脂肪组织脂联素mRNA表达量与BMI(r=-0·513,P<0·05)、VLDL-C(r=-0·733,P<0·01)显著负相关。结论肥胖症患者网膜脂肪组织脂联素mRNA表达水平显著降低,它可能在肥胖相关的代谢综合征的发病中起一定作用。     

2型糖尿病患者大网膜脂肪组织脂联素mRNA表达的研究

目的研究2型糖尿病（T2DM）患者大网膜脂肪组织脂联素mRNA的表达水平及其与腰围（WC）、BMI、腰臀比（WHR）、FPG、TG、TC、HDL-C、LDL-C、BP、病程等相关指标的关系。方法用半定量RT-PCR法检测T2DM患者（DM组）和非糖尿病患者（non-DM组）大网膜脂肪组织脂联素mRNA的表达水平。常规检测FPG、TG、TC、HDL-C、LDL-C、BP,计算BMI、WHR。结果与non-DM组相比,DM组大网膜脂肪组织脂联素mRNA表达水平显著下降（P〈0.05）,并与WC、TG、FPG、WHR明显负相关,其中以WC的相关性最大;未发现与BMI、HDL-C、LDL-C、TC及BP相关。结论T2DM患者大网膜脂肪组织脂联素mRNA表达显著降低;WC、TG、FPG、WHR、病程等临床指标可间接反映胰岛素抵抗程度,其中以WC的参考意义最大。     

脂联素及其受体mRNA表达与血清游离脂肪酸、肿瘤坏死因子α的研究

目的 了解肿瘤坏死因子-α(TNF-α)和游离脂肪酸(FFA)与脂联素及脂联素受体mRNA表达的关系.方法 19例肥胖和29例正常体重受试者,采用RT-PCR检测腹部皮下与大网膜脂肪组织中脂联素及其受体mRNA的表达水平,同时测定血清脂联素、TNF-α、FFA等指标.结果 (1)肥胖患者的血清TNF-α、FFA高于正常体重组;脂联素降低.(2)肥胖组中网膜脂肪组织脂联素mRNA表达量低于皮下脂肪组织和正常体重组网膜脂肪组织.(3)网膜脂肪组织脂联素mRNA表达量与脂联素水平呈负相关.(4)腹部皮下脂肪组织的脂联素受体1、脂联素受体2 mRNA表达水平与血清脂联素、FFA呈负相关.结论 肥胖人群的血清TNF-α、FFA升高,脂联素降低,且其网膜脂肪组织中脂联素mRNA表达量亦降低;血清FFA升高与腹部皮下脂联素受体表达下调相关.     

肥胖和2型糖尿病患者脂肪组织脂联素mRNA表达的研究

用实时定量PCR技术检测2型糖尿病患者(肥胖与非肥胖)和非2型糖尿病者皮下及大网膜脂联素mRNA表达量;ELISA法测血清脂联素浓度。皮下脂肪脂联素mRNA表达量高于大网膜;2型糖尿病、肥胖患者大网膜脂肪脂联素mRNA表达量对血清脂联素浓度有影响;性别可影响脂联索mRNA表达。     

妊娠期糖尿病患者脂肪组织脂联素mRNA表达与胰岛素抵抗的关系

目的 探讨妊娠期糖尿病（GDM）患者脂肪组织脂联素mRNA表达与胰岛素抵抗（IR）的关系.方法 检测GDM患者（GDM组） 的皮下与网膜脂肪脂联素mRNA、血脂、空腹胰岛素（FINS）、游离脂肪酸（FFA）及胰岛素抵抗指数（HOMA-IR）等,并与正常孕妇（NGT组）和非育龄择期手术者（对照组）进行比较.结果 GDM组、NGT组和对照组的皮下脂肪脂联素mRNA表达均高于其网膜脂肪水平;对照组、NGT组、GDM组皮下、网膜脂肪脂联素mRNA表达依次降低（P均＜0.01）.三组TG、LDL-C、FFA、FINS 和HOMA-IR比较均有统计学差异（P均＜0.01）.GDM组网膜脂肪脂联素mRNA表达与CRP、FPG、FINS、HOMA-IR和孕前BMI等呈负相关（P＜0.01或＜0.05）.结论 GDM患者的网膜脂肪脂联素mRNA表达降低与其IR及GDM发生有关.     

Ⅱ型糖尿病病人脂肪组织胰岛素受体底物1和含2个SH2结构的蛋白酪氨酸磷酸酶的蛋白表达

目的　研究Ⅱ型糖尿病患者脂肪组织胰岛素受体底物 1(IRS 1)及含 2个SH2 结构的蛋白酪氨酸磷酸酶 (SH PTP2 )蛋白表达 ,探讨脂肪组织产生胰岛素抵抗的分子机制。方法　用Western杂交检测Ⅱ型糖尿病患者腹部皮下与大网膜脂肪组织IRS 1、SH PTP2 的蛋白表达 ;同时比较患者自身皮下与大网膜内蛋白表达水平。结果　IRS 1蛋白表达 (A值 )在糖尿病患者皮下脂肪 (2 14± 0 6 7)、大网膜内 (3 2 5± 0 70 )均较对照组 [4 33± 0 5 7(P <0 0 0 1)、8 6 5± 2 85 (P <0 0 5 ) ]减少 ;而SH PTP2与对照组比较差异无显著性 (P >0 0 5 )。IRS 1蛋白表达在患者自身皮下脂肪 (1 0 9± 0 13)较大网膜(2 10± 0 2 2 )减少 (P <0 0 5 ) ;而SH PTP2 在皮下 (70 75± 2 18)则较大网膜 (4 3 6 9± 11 0 7)增加 (P <0 0 5 )。结论　Ⅱ型糖尿病患者脂肪组织IRS 1及SH PTP2 蛋白表达的异常改变可能是引起其产生胰岛素抵抗的机制之一 ;Ⅱ型糖尿病患者的腹部皮下脂肪和内脏脂肪一样存在胰岛素抵抗。     

维吾尔族肥胖患者脂肪和血清内脂素、脂联素的改变及相关因素

目的 探讨维吾尔族肥胖患者内脂素、脂联素(APN)在腹部网膜、皮下脂肪组织的表达和血清水平改变及其与体重指数(BMI)、腰臀围比(WHR)和血脂的关系.方法 用半定量RT-PCR方法检测41例肥胖患者和20例非肥胖对照脂肪组织内脂素和APN mRNA表达水平,ELISA法检测血清内脂素和APN浓度,并测量腰围(WC)、臀围(HC)、血压(BP)、空腹血糖(FPG)和血脂等.结果 ① 网膜脂肪组织内脂素mRNA表达水平在肥胖组与非肥胖对照组之间差异无显著性,肥胖组APN mRNA表达水平显著低于非肥胖对照组(P<0.05);内脂素、APN在两组网膜和皮下脂肪组织mRNA的表达水平均无显著性部位差异;血清内脂素肥胖组显著高于非肥胖对照组(P<0.05),APN在两组之间比较差异无显著性.② 肥胖组舒张压(DBP)和收缩压(SBP)均显著高于非肥胖对照组(P<0.01和P<0.01),高密度脂蛋白(HDL-C)明显低于非肥胖对照组(P<0.05).③ 网膜脂肪组织内脂素mRNA表达量与血清内脂素、BMI和TG显著正相关,APN mRNA表达量与血清APN显著正相关,与BMI、LDL-C显著负相关.结论 维吾尔族肥胖患者血清内脂素水平升高,网膜和皮下脂肪组织内脂素mRNA表达水平无显著性部位差异;APN mRNA在网膜脂肪组织的表达显著降低,内脂素和脂联素可能在维吾尔人中心性肥胖相关的代谢紊乱性疾病中起一定作用.     

2型糖尿病患者内脂素在网膜脂肪组织中的表达及与血清浓度的关系

目的探讨内脂素基因在2型糖尿病患者网膜脂肪组织中的表达情况及其与血清浓度的关系。方法选取2型糖尿病患者及健康对照者各60例,用Northern b lot印迹技术检测两组网膜脂肪组织内脂素mRNA的表达水平,并测定血浆内脂素浓度、空腹血糖、OGTT 2 h血糖、空腹胰岛素、血脂及其他生化指标。结果 2型糖尿病组网膜组织的内脂素mRNA表达显著高于对照组（P〈0.01）。两组网膜组织中内脂素mRNA表达与内脂素血清浓度呈正相关。结论 T2DM患者网膜内脂素mRNA表达量较对照组升高,且与血清浓度呈正相关。     

肥胖患者大网膜脂肪脂联素mRNA表达及相关因素的研究

选择43例择期外科手术患者，用RT-PCR法检测大网膜脂肪组织脂联素表达水平。发现肥胖患者的大网膜脂肪组织中脂联素表达明显降低，腹型肥胖、胰岛素抵抗以及肿瘤坏死因子-α是大网膜脂肪组织脂联素表达水平的主要影响因素。     

血浆脂联素与2型糖尿病胰岛素抵抗关系的研究

目的　测定 2型糖尿病患者血浆脂联素的水平 ,并分析它与体重指数、血糖、胰岛素、血脂和胰岛素抵抗的关系 ,从而探讨脂联素在糖尿病发病中的作用。方法　健康对照组 2 8例 ,2型糖尿病组 60例 ,根据体重指数又将糖尿病组分为非肥胖糖尿病组 3 0例 (BMI <2 5kg/m2 )和肥胖糖尿病组 3 0例 (BMI >2 5kg/m2 )。用ELISA方法检测空腹血浆脂联素浓度 ,同时测定各组的空腹血糖、胰岛素、血脂的水平 ;根据HOMA模型提出的公式 ,计算分析胰岛素抵抗指数 ,并分析各指标间的相关性。结果　 (1)糖尿病各组血浆脂联素的水平明显低于正常对照组 ,且肥胖糖尿病组脂联素的水平低于非肥胖组 ,差异均有显著性 (P 0 .0 1) ;(2 )血浆脂联素浓度与体重指数、空腹胰岛素、胰岛素抵抗指数 (IR)、甘油三酯呈显著负相关。结论　脂联素参与了胰岛素抵抗的发生过程 ,与糖尿病的发生发展密切相关 ;脂联素可作为评价胰岛素抵抗程度的一种新的敏感指标     

Adiponectin mRNA levels in the abdominal adipose depots of nondiabetic women

BACKGROUND: The human adiponectin gene has been implicated in the pathophysiology of obesity, type II diabetes mellitus, dyslipidemia and atherosclerosis. Investigation of the physiological functions of the adiponectin gene in humans was mainly conducted at the levels of plasma proteins or DNA polymorphisms. The depot-specific adiponectin mRNA levels also could be relevant to these physiological functions. OBJECTIVES: The relation between the adipose depot-specific adiponectin mRNA expression levels and various metabolic factors, including BMI, fasting plasma glucose, insulin, triglycerides (TGs) and HDL-cholesterol and insulin resistance index by HOMA, was investigated among 66 nondiabetic women using quantitative real-time PCR. RESULTS: The subcutaneous relative adiponectin mRNA levels (SRAmR) correlated significantly with the omental relative adiponectin mRNA levels (ORAmR) (gamma=0.468, P=0.0001). The SRAmR correlated inversely with the fasting plasma glucose with a borderline significance (gamma=-0.35, P=0.058). On the other hand, the ORAmR correlated negatively with serum TG levels with the adjustment for age (gamma=-0.33, P=0.007) or age plus BMI (gamma=-0.27, P=0.027). CONCLUSION: These results indicate that the adiponectin mRNA levels in different adipose depots were at least related to certain phenotypes of metabolic syndrome. The expression levels of adiponectin in the omental adipose depots are related to TG metabolism.     

Human adipose tissue cannabinoid receptor 1 gene expression is not related to fat cell function or adiponectin level

CONTEXT: The cannabinoid receptor 1 gene (CNR1) is implicated in adipocyte function. OBJECTIVE: We investigated human adipose tissue CNR1 mRNA in relation to obesity, clinical and metabolic variables, adipocyte function, and adiponectin (ADIPOQ) levels. METHODS: We assessed sc fat biopsies from 96 obese and nonobese subjects and omental fat biopsies from 82 obese and nonobese subjects. RESULTS: The sc and omental adipose CNR1 gene expression were similar in obese and nonobese subjects. No association between either sc or omental adipose CNR1 mRNA levels and body mass index, waist circumference, plasma levels of glucose and insulin, lipids, or blood pressure was found. The sc and omental maximal adrenergic lipolytic activation as well as lipolytic adrenoceptor sensitivity were not related to CNR1 gene expression. Lipogenesis in sc adipocytes also showed no association with CNR1 mRNA levels. Finally, no relation was found between adipose CNR1 gene expression and ADIPOQ mRNA, adipose tissue adiponectin secretion, or circulating adiponectin. CONCLUSION: We found no association of human adipose tissue CNR1 mRNA expression with measures of body fat, metabolic parameters, fat cell function, or ADIPOQ expression. These data do not suggest a major role of human adipose CNR1 in fat cell function or metabolic disease development.     

非酒精性脂肪肝患者胰岛素抵抗与脂联素基因表达的关系

目的探讨NAFLD患者胰岛素抵抗（IR）与脂肪组织脂联素基因表达的关系。方法用SYBR GreenI实时定量RT-PCR方法检测脂肪组织脂联素mRNA的表达水平，用稳态模型法计算IR指数。结果肥胖和非肥胖NAFLD患者及对照组IR指数分别为：3．0±0．8、2．8±0．9和2．0±0．6、1．2±0．5，其脂肪组织脂联素基因表达和血浆脂联素浓度较对照各组显著降低（P〈0．05），IR与脂联素基因表达（r=0．5，P〈0．05）和血浆脂联素浓度负相关（，=0．4，P〈0．05），与血清甘油三酯正相关（r=0．3，P〈0．05）。结论NAFLD患者的IR与脂肪组织脂联素基因低表达有关，脂联素基因低表达在IR和NAFLD发病中起了一定作用。     

Insulin effect on adipose tissue (AT) adiponectin expression is regulated by the insulin resistance status of the patients

Objective  The objective of the present study was to determine a possible depot-specific effect of insulin-stimulation on adiponectin gene expression in adipose tissue (AT) explants from subcutaneous and visceral AT. A secondary aim was to analyse the associations of adiponectin plasma levels, as well as control and insulin-stimulated gene expression levels with different features of the metabolic syndrome.
Design  Visceral and subcutaneous AT biopsies were obtained from 20 subjects (10 men and 10 women) with morbid obesity. Metabolic syndrome and other clinical features were studied. Adiponectin expression from isolated adipocytes was measured both in control and after insulin-stimulation conditions by quantitative PCR.
Results  Subcutaneous adipocytes expressed significantly higher amounts of adiponectin mRNA than visceral tissue ( P =  0·027). Insulin increased adiponectin expression specifically in the omental tissue ( P =  0·011). In these patients, waist : hip ratio was directly correlated with adiponectin expression in the visceral depot ( r  = 0·660; P  = 0·014), while fasting glucose levels were inversely associated with adiponectin mRNA in the subcutaneous tissue ( r  = – 0·604; P  = 0·022). Adiponectin expression after addition of insulin was positively correlated with some metabolic risk factors (cholesterol, LDL-cholesterol, insulin, C-peptide). Interestingly, local insulin induced an up-regulation of adiponectin expression in the AT of those patients with higher metabolic syndrome disturbances.
Conclusions  Our results clearly demonstrate that insulin exerts a stimulating effect on adiponectin gene expression in a depot-specific manner. The AT response to insulin stimulus depends on the physiopathological situation, being higher in those individuals with impaired insulin-sensitivity and lipid metabolism.     

Association between low SIRT1 expression in visceral and subcutaneous adipose tissues and metabolic abnormalities in women with obesity and type 2 diabetes

Aims

To assess the importance of adipose tissue sirtuin 1 (SIRT1) in the regulation of whole-body metabolism in humans with obesity and type 2 diabetes.

Methods

In total, 19 non-diabetic obese women, 19 type 2 diabetic women undergoing gastric bypass surgery, and 27 normal-weight women undergoing gynecological surgery (total 65 women) were enrolled. Their anthropometric variables, abdominal fat distribution and metabolic parameters, serum adiponectin concentrations, and SIRT1 mRNA and protein and adiponectin mRNA expressions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured.

Results

SIRT1 mRNA levels in VAT and SAT were similar and these levels were suppressed in obese and type 2 diabetic women compared to normal-weight subjects. These decreases in SIRT1 expression were observed in both adipocytes and non-fat cells. There was a strong association between adipose tissue SIRT1 mRNA and protein levels. Adipose SIRT1 expression correlated inversely with HOMA-IR and other insulin resistance-related parameters. Adipose SIRT1 and adiponectin mRNA expression correlated very strongly and positively. SIRT1 mRNA level in VAT correlated inversely with visceral obesity whereas its expression in SAT correlated negatively with body mass index.

Conclusions

Adipose tissue SIRT1 may play a key role in the regulation of whole body metabolic homeostasis in humans. Downregulation of SIRT1 in VAT may contribute to the metabolic abnormalities that are associated with visceral obesity.     

2型糖尿病大鼠脂肪组织脂联素和骨骼肌组织脂联素受体R1基因表达的变化

半定量RT-PCR检测2型糖尿病大鼠模型脂肪组织脂联素及骨骼肌组织脂联素受体R1 mRNA表达。与正常大鼠比较，糖尿病大鼠骨骼肌组织脂联素受体R1基因表达无改变。糖尿病大鼠血清脂联素水平下降是由脂肪组织脂联素mRNA表达降低引起的，罗格列酮治疗可以使之改善。     

Type 2 diabetes mellitus is characterized by reduced postprandial adiponectin response: a possible link with diabetic postprandial dyslipidemia

We investigated postprandial plasma and adipose tissue (AT) adiponectin changes in relation to obesity and type 2 diabetes mellitus. Fasting and 6 hours after a standard fat-rich meal blood samples (adiponectin, glucose, insulin, lipids) and needle biopsies of abdominal subcutaneous AT (adiponectin messenger RNA, lipoprotein lipase activity) were taken in 10 obese diabetic (OD), 11 obese nondiabetic (OND), and 11 normal-weight control (C) men. The OD and OND subjects had similar adiposity (body mass index, waist circumference) and insulin resistance (hyperinsulinemic euglycemic clamp). Fasting plasma adiponectin and AT gene expression were not significantly different between groups. After meal, plasma adiponectin decreased in OD but significantly increased in OND and C, the changes being significantly different between groups (analysis of variance, P = .01); adiponectin messenger RNA decreased in OD (−0.27 ± 0.25 AU, P = .01) but was unchanged in OND (P = .59) and C (P = .45). After meal, plasma adiponectin correlated inversely with triglyceride and cholesterol concentrations in chylomicrons and large very low-density lipoprotein, and directly with AT lipoprotein lipase activity (P < .05 for all). Type 2 diabetes mellitus is associated with lower postprandial plasma levels and AT gene expression of adiponectin independently of degree of adiposity and whole-body insulin sensitivity. In patients with diabetes, this may exacerbate postprandial abnormalities of lipoprotein metabolism.     

Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFalpha, and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.