Borst Stephen E, Conover Christine F
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32608-1197, USA.
Life Sci. 2005 Sep 9;77(17):2156-65. doi: 10.1016/j.lfs.2005.03.021.
In several strains of genetically obese and insulin resistant rodents, adipose tissue over expresses mRNA for tumor necrosis factor alpha (TNF-alpha). Our purpose was to determine whether tissue expression of TNF-alpha protein is elevated in rats that are made obese and insulin resistant by administration of a high-fat diet. Young Wistar rats weighing approximately 50 g were fed for 39 days with either normal rat chow (12.4% fat) or a high-fat diet (50% fat). After 33 days, glucose tolerance was assessed and after 39 days, insulin-stimulated transport of [3H]-2-deoxyglucose was assessed in isolated strips of soleus muscle. Rats on the high-fat diet consumed slightly fewer calories but became obese, displaying significant approximately 2-fold increases in the mass of both visceral and subcutaneous fat depots. High-fat feeding also caused a moderate degree of insulin resistance. Fasting serum insulin was significantly increased, as were insulin and glucose concentrations following glucose loading. In isolated strips of soleus muscle, the high-fat diet produced a trend toward a 33% decrease in the insulin-stimulated component of glucose transport (p=0.064). Western analysis of muscle, liver and fat revealed two forms of TNF-alpha, a soluble 17 Kd form (sTNF-alpha) and a 26 Kd membrane form (mTNF-alpha). Both sTNF-alpha and mTNF-alpha were relatively abundant in fat; whereas sTNF-alpha was the predominant form present in muscle and liver. High-fat feeding caused a significant 2-fold increase in muscle sTNF-alpha, along with a trend toward a 54% increase in visceral fat sTNF-alpha (p=0.055). TNF-alpha was undetectable in serum. We conclude that muscle over expression of TNF-alpha occurs during the development of diet-induced obesity and may, in part cause insulin resistance by an autocrine mechanism.
在几种遗传性肥胖和胰岛素抵抗的啮齿动物品系中，脂肪组织中肿瘤坏死因子α（TNF-α）的mRNA表达过高。我们的目的是确定通过给予高脂饮食使大鼠肥胖和胰岛素抵抗后，TNF-α蛋白的组织表达是否升高。将体重约50克的年轻Wistar大鼠用普通大鼠饲料（脂肪含量12.4%）或高脂饮食（脂肪含量50%）喂养39天。33天后评估葡萄糖耐量，39天后在分离的比目鱼肌条中评估胰岛素刺激的[3H]-2-脱氧葡萄糖转运。高脂饮食组的大鼠摄入的热量略少，但变得肥胖，内脏和皮下脂肪库的质量显著增加了约2倍。高脂喂养还导致了中度的胰岛素抵抗。空腹血清胰岛素显著升高，葡萄糖负荷后胰岛素和葡萄糖浓度也升高。在分离的比目鱼肌条中，高脂饮食使胰岛素刺激的葡萄糖转运成分有降低33%的趋势（p = 0.064）。对肌肉、肝脏和脂肪进行的蛋白质免疫印迹分析显示有两种形式的TNF-α，一种可溶性的17千道尔顿形式（sTNF-α）和一种26千道尔顿的膜结合形式（mTNF-α）。sTNF-α和mTNF-α在脂肪中都相对丰富；而sTNF-α是肌肉和肝脏中的主要形式。高脂喂养使肌肉中的sTNF-α显著增加了2倍，同时内脏脂肪中的sTNF-α有增加54%的趋势（p = 0.055）。血清中未检测到TNF-α。我们得出结论，在饮食诱导的肥胖发展过程中，肌肉中TNF-α表达过高，可能部分通过自分泌机制导致胰岛素抵抗。
