Hotamisligil G S, Arner P, Atkinson R L, Spiegelman B M
Department of Nutrition, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Diabetes. 1997 Mar;46(3):451-5. doi: 10.2337/diab.46.3.451.
Previous studies have shown that tumor necrosis factor (TNF)-alpha production from adipose tissue is elevated in rodent and human obesity and plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and protein levels were similar in these subjects. TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-alpha mRNA expression in fat tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-alpha.
以往研究表明，在啮齿动物和人类肥胖症中，脂肪组织产生的肿瘤坏死因子（TNF）-α会升高，并且在实验动物模型的胰岛素抵抗中起重要作用。在本研究中，我们检测了人类肥胖症中两种TNF受体（TNFR1和TNFR2）的脂肪表达情况，结果表明，相对于瘦的对照受试者，肥胖女性受试者脂肪组织中TNFR2 mRNA的表达量约多两倍，循环中可溶性TNFR2的含量约多六倍。相比之下，这些受试者中TNFR1的表达和蛋白水平相似。脂肪组织中TNFR2的表达水平与体重指数（r = 0.65，P < 0.001）、高胰岛素血症水平（P < 0.001，胰岛素抵抗的间接指标）以及脂肪组织中TNF-α mRNA的表达水平（r = 0.56，P < 0.001）密切相关。这些结果表明，TNFR2可能通过调节TNF-α的作用在人类肥胖症中发挥作用。
