Pape M E, Kim K H
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907.
Mol Endocrinol. 1988 May;2(5):395-403. doi: 10.1210/mend-2-5-395.
Tumor necrosis factor (TNF) is secreted by macrophages in response to various stimuli and blocks lipid accumulation during the conversion of preadipocytes to adipocytes in culture. In the present report, we investigate the effect of recombinant TNF on the expression of acetyl-coenzyme-A (CoA) carboxylase, the rate-limiting enzyme for long-chain fatty acid biosynthesis. We used a preadipocyte cell line, 30A-5, derived from 10T1/2 mouse fibroblasts after treatment with 5-azacytidine. Treatment of the preadipocyte cell line with dexamethasone and insulin triggers the conversion of these cells to mature adipocytes as evidenced by the accumulation of lipid. The mRNA and enzyme levels of acetyl-CoA carboxylase as well as the enzyme activity increase markedly during the conversion process. TNF prevents the conversion of preadipocytes to adipocytes with a concomitant inhibition in the accumulation of acetyl-CoA carboxylase mRNA and decrease in enzyme activity. This observed reduction in acetyl-CoA carboxylase mRNA levels is reversible upon removal of TNF. Acetyl-CoA carboxylase mRNA levels and enzyme activity also decrease when fully differentiated adipocytes are exposed to TNF but to a much lesser extent. These results suggest that TNF affects de novo lipid synthesis in part by altering the mRNA levels of acetyl-CoA carboxylase.
肿瘤坏死因子（TNF）由巨噬细胞在各种刺激下分泌，并在培养过程中阻止前脂肪细胞向脂肪细胞转化时的脂质积累。在本报告中，我们研究了重组TNF对乙酰辅酶A（CoA）羧化酶表达的影响，乙酰辅酶A羧化酶是长链脂肪酸生物合成的限速酶。我们使用了一种前脂肪细胞系30A - 5，它是由5 - 氮杂胞苷处理后的10T1/2小鼠成纤维细胞衍生而来。用地塞米松和胰岛素处理前脂肪细胞系会触发这些细胞向成熟脂肪细胞的转化，脂质积累证明了这一点。在转化过程中，乙酰辅酶A羧化酶的mRNA和酶水平以及酶活性显著增加。TNF阻止前脂肪细胞向脂肪细胞的转化，同时抑制乙酰辅酶A羧化酶mRNA的积累并降低酶活性。去除TNF后，观察到的乙酰辅酶A羧化酶mRNA水平的降低是可逆的。当完全分化的脂肪细胞暴露于TNF时，乙酰辅酶A羧化酶mRNA水平和酶活性也会降低，但程度要小得多。这些结果表明，TNF部分通过改变乙酰辅酶A羧化酶的mRNA水平来影响从头脂质合成。
