Hube F, Birgel M, Lee Y M, Hauner H
Diabetes Research Institute at the Heinrich-Heine-University, Düsseldorf, Germany.
Eur J Clin Invest. 1999 Aug;29(8):672-8. doi: 10.1046/j.1365-2362.1999.00520.x.
Tumour necrosis factor alpha (TNF) mRNA expression has been reported to be up-regulated in adipose tissue from several rodent models of obesity and diabetes and from obese humans. This elevated expression has been assumed to be associated with the development of insulin resistance. However, the biological signal of TNF may be influenced by the expression of the two TNF receptors: the p60 TNF receptor, TNFR60, and the p80 TNF receptor, TNFR80.
The aim of this study was to investigate the mRNA expression pattern of the two TNF receptors and their ligand in two adipose tissue depots of glucose-tolerant obese women [n = 18, body mass index (BMI) 48.2 +/- 8.4 kg m-2], obese women with impaired glucose tolerance or overt non-insulin-dependent diabetes mellitus (NIDDM) (n = 10, BMI 49.1 +/- 11.6 kg m-2) and healthy non-obese control subjects (n = 12, BMI 25.8 +/- 2.7 kg m-2). RNA expression was assessed by a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique.
The mean mRNA levels of both TNF receptors were two- to threefold higher in adipose tissue samples from the obese than from the non-obese women (P < 0.01 for each). Although TNFR60 mRNA did not vary within each obese group, there was a wide variation in the levels of TNFR80 mRNA and of TNF mRNA. A comparison of the expression levels between the subcutaneous abdominal and the omental adipose tissue depots showed significantly higher expression in the former. The TNFR60 expression level was positively correlated with BMI and fat cell size, whereas TNFR80 and TNF mRNA levels showed positive associations with serum insulin and triglyceride concentrations. No significant differences in the expression levels were observed between obese individuals with and without impaired glucose tolerance/NIDDM.
These results indicate that severe obesity in women is characterized by increased amounts of the two TNF receptor mRNAs. The role of this up-regulation for the development of obesity-associated insulin resistance remains to be elucidated.
据报道，在几种肥胖和糖尿病的啮齿动物模型以及肥胖人类的脂肪组织中，肿瘤坏死因子α（TNF）mRNA表达上调。这种表达升高被认为与胰岛素抵抗的发展有关。然而，TNF的生物学信号可能受两种TNF受体表达的影响：p60 TNF受体（TNFR60）和p80 TNF受体（TNFR80）。
本研究的目的是调查糖耐量正常的肥胖女性[18例，体重指数（BMI）48.2±8.4kg/m²]、糖耐量受损或明显非胰岛素依赖型糖尿病（NIDDM）的肥胖女性（10例，BMI 49.1±11.6kg/m²）以及健康非肥胖对照受试者（12例，BMI 25.8±2.7kg/m²）的两个脂肪组织库中两种TNF受体及其配体的mRNA表达模式。通过半定量逆转录聚合酶链反应（RT-PCR）技术评估RNA表达。
肥胖女性脂肪组织样本中两种TNF受体的平均mRNA水平比非肥胖女性高两到三倍（每种情况P<0.01）。虽然TNFR60 mRNA在每个肥胖组内没有变化，但TNFR80 mRNA和TNF mRNA水平存在很大差异。比较腹部皮下和网膜脂肪组织库之间的表达水平，前者表达明显更高。TNFR60表达水平与BMI和脂肪细胞大小呈正相关，而TNFR80和TNF mRNA水平与血清胰岛素和甘油三酯浓度呈正相关。糖耐量受损/NIDDM的肥胖个体与未受损的肥胖个体之间在表达水平上未观察到显著差异。
这些结果表明，女性严重肥胖的特征是两种TNF受体mRNA的量增加。这种上调在肥胖相关胰岛素抵抗发展中的作用仍有待阐明。
