Effect of tumor necrosis factor on acetyl-coenzyme A carboxylase gene expression and preadipocyte differentiation.
Effect of tumor necrosis factor on acetyl-coenzyme A carboxylase gene expression and preadipocyte differentiation.
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DOI：
10.1210/mend-2-5-395
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发表时间：
1988-05
影响因子：
--
通讯作者：
M. Pape;K. H. Kim
中科院分区：
文献类型：
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作者：
M. Pape;K. H. Kim
肿瘤坏死因子（Tumor necrosis factor， TNF）由巨噬细胞分泌，以响应各种刺激，并在培养过程中阻止脂肪细胞向脂肪细胞转化过程中的脂质积累。在本报告中，我们研究了重组TNF对长链脂肪酸生物合成的限速酶乙酰辅酶- a （CoA）羧化酶表达的影响。我们使用了一种前脂肪细胞系，30A-5，来源于10T1/2小鼠成纤维细胞，经过5-氮胞苷处理。地塞米松和胰岛素处理前脂肪细胞系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mRNA和酶水平显著升高，酶活性显著升高。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的积累和酶活性的降低。这种观察到的乙酰辅酶a羧化酶mRNA水平的降低在去除TNF后是可逆的。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通过改变乙酰辅酶a羧化酶的mRNA水平来部分影响新生脂质合成。
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.