Halle M, Berg A, Northoff H, Keul J
Dept. of Rehabilitation, Prevention, and Sports Medicine, Freiburg University Hospital, Germany.
Exerc Immunol Rev. 1998;4:77-94.
Obesity is associated with an increased incidence of insulin resistance, dyslipoproteinemia, and hypercoagulability. In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans. Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary cytokine structure whose concentrations correlate with the amount of fat tissue. Increased leptin levels downregulate appetite and increase sympathetic activity and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and serum leptin levels and is associated with improved insulin sensitivity and lipid metabolism. Although exercise has also been shown to reduce leptin levels, an influence on TNF-a expression in adipocytes or muscle cells has not yet been demonstrated.
肥胖与胰岛素抵抗、血脂异常和高凝状态的发生率增加有关。在最近建立的体重控制和代谢调节假说中，脂肪细胞分泌瘦素并在局部表达肿瘤坏死因子-α（TNF-α），后者负责代谢性心血管危险因素的表达。肥胖动物和人类的脂肪组织中TNF-α mRNA表达和TNF-α蛋白显著增加。TNF-α表达升高通过下调胰岛素受体的酪氨酸激酶活性和降低葡萄糖转运蛋白4（GLUT-4）的表达来诱导胰岛素抵抗。TNF-α还降低白色脂肪细胞中的脂蛋白脂肪酶活性，刺激肝脏脂肪分解，并增加脂肪细胞中纤溶酶原激活物抑制剂-1的含量。此外，脂肪细胞分泌瘦素，这是一种具有二级细胞因子结构的分子，其浓度与脂肪组织量相关。瘦素水平升高会下调食欲，并增加下丘脑的交感神经活动和产热。饮食诱导的体重减轻会降低脂肪组织TNF-α表达和血清瘦素水平，并与胰岛素敏感性和脂质代谢改善有关。虽然运动也已被证明可降低瘦素水平，但尚未证实其对脂肪细胞或肌肉细胞中TNF-α表达的影响。
