Grunfeld C, Adi S, Soued M, Moser A, Fiers W, Feingold K R
Department of Medicine, University of California, San Francisco.
Cancer Res. 1990 Jul 15;50(14):4233-8.
The significance of potential second messengers as mediators of the metabolic effects of tumor necrosis factor (TNF) was explored by studying their role in stimulating hepatic lipogenesis. Platelet-activating factor and prostaglandins have previously been suggested to mediate some of the toxic effects of TNF. An inhibitor of platelet-activating factor (WEB 2086) and two inhibitors of the synthesis of prostaglandins (ibuprofen and aspirin) had no effect on the ability of TNF to increase hepatic lipogenesis or serum triglyceride levels in the rat. Another inhibitor of the toxic effects of TNF, pentoxifylline, also had no effect on lipid metabolism in the rat. Catecholamines are increased after TNF administration, but alpha- and beta-adrenergic blockade did not prevent the lipogenic effects of TNF. However, interleukin 6, a cytokine whose synthesis and secretion are induced by TNF, is able to acutely stimulate hepatic lipogenesis in mice. Interleukin 6 stimulates hepatic lipogenesis by increasing hepatic citrate concentrations, the same mechanism by which TNF stimulates hepatic lipogenesis. These data suggest that interleukin 6, but not platelet-activating factor, prostaglandins, or catecholamines, could potentially mediate the lipogenic effects of TNF.
通过研究潜在第二信使在刺激肝脏脂肪生成中的作用，探讨了其作为肿瘤坏死因子（TNF）代谢效应介质的意义。血小板活化因子和前列腺素此前被认为介导TNF的一些毒性作用。血小板活化因子抑制剂（WEB 2086）以及两种前列腺素合成抑制剂（布洛芬和阿司匹林）对TNF增加大鼠肝脏脂肪生成或血清甘油三酯水平的能力没有影响。另一种TNF毒性作用抑制剂己酮可可碱对大鼠脂质代谢也没有影响。给予TNF后儿茶酚胺增加，但α和β肾上腺素能阻断并不能阻止TNF的脂肪生成作用。然而，白细胞介素6是一种其合成和分泌由TNF诱导的细胞因子，能够急性刺激小鼠肝脏脂肪生成。白细胞介素6通过增加肝脏柠檬酸浓度来刺激肝脏脂肪生成，这与TNF刺激肝脏脂肪生成的机制相同。这些数据表明，白细胞介素6而非血小板活化因子、前列腺素或儿茶酚胺可能介导TNF的脂肪生成作用。
