Skolnik E Y, Marcusohn J
New York University Medical Center, Skirball Institute, NY 10016, USA.
Cytokine Growth Factor Rev. 1996 Aug;7(2):161-73. doi: 10.1016/1359-6101(96)00021-4.
Adipocytes produce a variety of molecules that are capable of functioning in both a paracrine and autocrine fashion. Tumor necrosis factor (TNF) is one of the proteins produced by adipocytes that has been shown to regulate adipocyte function. Interestingly, adipocyte expression of TNF increases with increasing adipocyte mass and expression of TNF is increased in adipocytes isolated from several genetic models of rodent obesity and from obese humans. This finding has led to the idea that TNF produced by adipocytes functions as a local "adipostat" to limit fat accumulation. Increased production of TNF by adipocytes, however, may contribute to insulin resistance in obesity and in non-insulin-dependent diabetes mellitus (NIDDM). TNF has been shown to inhibit insulin-simulated tyrosine phosphorylation of both the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and to stimulate downregulation of the insulin-sensitive glucose transporter, GLUT4, in adipocytes. These findings raise the possibility that pharmacological inhibition of TNF may provide a novel therapeutic target to treat patients with NIDDM.
脂肪细胞产生多种能够以旁分泌和自分泌方式发挥作用的分子。肿瘤坏死因子（TNF）是脂肪细胞产生的蛋白质之一，已被证明可调节脂肪细胞功能。有趣的是，TNF在脂肪细胞中的表达随着脂肪细胞量的增加而增加，并且在从几种啮齿动物肥胖遗传模型和肥胖人类分离出的脂肪细胞中，TNF的表达也增加。这一发现引发了这样一种观点，即脂肪细胞产生的TNF作为一种局部“脂肪稳态调节因子”来限制脂肪堆积。然而，脂肪细胞中TNF产生的增加可能导致肥胖症和非胰岛素依赖型糖尿病（NIDDM）中的胰岛素抵抗。TNF已被证明可抑制胰岛素受体（IR）和胰岛素受体底物（IRS）-1的胰岛素模拟酪氨酸磷酸化，并刺激脂肪细胞中胰岛素敏感的葡萄糖转运蛋白GLUT4的下调。这些发现增加了这样一种可能性，即对TNF的药理学抑制可能为治疗NIDDM患者提供一种新的治疗靶点。
