肥胖和2型糖尿病患者脂肪组织网膜素的mRNA表达

Expression of omentin in adipose tissues in obese and type 2 diabetic patients

目的研究不同糖调节和体重人群脂肪组织网膜素表达差异及其与血清网膜素、体脂参数、糖脂代谢、胰岛素抵抗等的相关性。方法36例外科择期手术患者分为正常糖调节正常体重（NGR-NW）组，正常糖调节超重／肥胖（NGR-OW／OB）组和2型糖尿病超重／肥胖（T2DM-OW／OB）组。采用实时定量PCR方法测定腹部皮下和网膜脂肪组织网膜素mRNA水平。用ELISA法检测空腹血清网膜素水平，同时检测空腹血糖（FPG）、口服葡萄糖耐量试验2h血糖（2hPG）、糖化血红蛋白（HbA1c）、血脂各项指标及空腹胰岛素（FINS），计算体重指数（BMI）和腰臀比值（WHR），并以稳态模型计算胰岛素抵抗指数（HOMA—IR）。结果网膜脂肪组织网膜素mRNA水平显著高于皮下脂肪组织[1．52±0．32比0．019±0．006，P〈0．01（均以网膜素／β-肌动蛋白来定量）]；男性和女性网膜素mRNA水平无差异（1．46±0．31比1．58±0．29，P=0．416）；NGR-OW／OB组网膜素mRNA水平显著低于NGR．NW组（1．18±0．29比1．52±0．32，P〈0．05），T2DM．OW／OB组网膜素mRNA水平显著低于NGR-NW组和NGR．OW／OB组（分别为0．98±0．37比1．52±0．32和0．98±0．37比1．18±0．29，均P〈0．05）；相关分析显示，网膜脂肪组织网膜素mRNA水平与HOMA—IR、腰围、WHR、甘油三酯、BMI、FINS呈显著负相关（r=-0．196～-0．283，均P〈0．05），与血清网膜素、HDL—C呈显著正相关（r=0．588、0．242，均P〈0．05）；多元逐步回归分析发现，血清网膜素、HOMA-IR和腰围是网膜素mRNA水平的独立相关因素（相关系数r^2=0．145、0．190、0．224，均P〈0．05）。结论网膜素在不同个体的差异表达可能参与构成胰岛素抵抗综合征的病理生理基础。

Objective To analyze the mRNA expression of omentin mRNA level in subcutaneous and omental adipose tissues of normal, obese, and type 2 diabetic individuals and to investigate the relationship between omentin mRNA expression and serum omentin level, body fat parameters, glucose and lipid metabolism, and insulin resistance indexes. Methods 36 patients with benign diseases undergoing selective abdominal operation, 19 males and 17 females, aged 20- 65, included 12 with normal glucose regulation and normal weight （NGR-NW group）, 12 with normal glucose regulation and overweight/obesity （NGR-OW/OB group）, and 12 with type 2 diabetes and overweight/obesity （T2DM-OW/OB group）. Abdominal subcutaneous and omental adipose tissues were obtained during operation. Real-time quantitative PCR was used to measure the omentin mRNA level . The level of fasting serum omentin was measured by ELISA. Meanwhile blood glucose,HbAlc, lipids and insulin levels were measured. Body weight, BMI and waist hip ratio （WHR） were evaluated and insulin sensitivity was assessed by homeostasis model assessment insulin resistance index （HOMA-IR）. Results The omentin mRNA level in omental adipose tissue of the NGR-NW group was （1.52 ±0.32）, significantly higher than that in subcutaneous adipose tissue [ （0. 019 ± 0.006） ,P 〈0.01 ]. The omentin mRNA level of the males was （ 1.46 ± 0.31 ）, not statistically different from that of the female [ （1.58 ±0.29） ,P =0. 4161. The omentin mRNA level of the NGR-OW/OB group was （ 1.18 ± 0.29）, significantly lower than that of the NGR-NW group [ （ 1.52 ± 0.32） ,P 〈 0.05 ], and the omentin mRNA level of the T2DM-OW/OB group was （0.98 ± 0.37 ）, both significantly lower than those of the other 2 groups （ both P 〈 0.05 ）. Partial correlation analysis showed that the omentin mRNA was negatively correlated with HOMA-IR, body weight, WHR, triglyceride, BMI, and fasting insulin, and positively correlated to serum omentin level and HDL-C. Multiple linear regression analysis showed that serum omentin level, HOMA-IR, and body weight were independent variables of omentin. Conclusion Omentin mRNA is highly expressed in omental adipose tissue. The omentin mRNA expression level decreases in the overweight/obese individuals and decreases further when overweight/obesity is combined with type 2 diabetes. Omentin mRNA is positively correlated to serum omentin level, obese indexes,insulin resistance, and lipid metabolism parameters. Decreased omentin gene expression may contribute to the underlying pathophysiology of insulin resistance syndrome.