TUMOR NECROSIS FACTOR STIMULATES HEPATIC LIPID-SYNTHESIS AND SECRETION
TUMOR NECROSIS FACTOR STIMULATES HEPATIC LIPID-SYNTHESIS AND SECRETION
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DOI：
10.1210/endo-124-5-2336
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发表时间：
1989-05-01
期刊：
影响因子：
4.8
通讯作者：
GRUNFELD, C
中科院分区：
文献类型：
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作者：
FEINGOLD, KR;SERIO, MK;GRUNFELD, C
先前的研究表明，肿瘤坏死因子(TNF)可以显著增加血清甘油三酯水平，刺激肝脏新生脂肪酸的合成。我们现在证明，在给予肿瘤坏死因子60-90分钟后，饲喂食物的大鼠肝脏中甘油与甘油三酯的结合增加了57%。此外，经肿瘤坏死因子处理的动物，血清中标记脂类的数量增加了96%。在高蔗糖饮食的大鼠中，肿瘤坏死因子还能显著增加肝脏脂肪合成和血清中标记脂类的数量。此外，使用Triton WR-1339方法，在给药后1-2小时内，肝脏总甘油三酯分泌量增加52%。相反，在给予肿瘤坏死因子前禁食的动物中，没有观察到血清甘油三酯水平的特征性升高，也没有观察到甘油掺入肝脂或循环中标记的脂类数量增加。至注射后17h，甘油在肝脂中的积聚不再增加，血清中标记脂类的量不再增加。这些结果表明，除了肿瘤坏死因子能强烈刺激新生脂肪酸的合成外，肿瘤坏死因子还能刺激肝脏甘油三酯的合成。肝脏甘油三酯合成的增加导致进入循环的脂质分泌增加。这些观察结果有力地支持了我们的假设，即肿瘤坏死因子诱导的肝脏脂质合成和分泌的刺激导致了肿瘤坏死因子诱导的高脂血症。
Previous studies have shown that tumor necrosis factor (TNF) administration acutely increases serum triglyceride levels and stimulates hepatic de novo fatty acid synthesis. We now demonstrate that 60-90 min after TNF administration the incorporation of glycerol into triglycerides in the liver is increased 57% in chow-fed rats. Additionally, the quantity of labeled lipid in serum is increased 96% in the TNF-treated animals. TNF also acutely increases hepatic lipid synthesis and the quantity of labeled lipids in serum in rats fed a high sucrose diet. Moreover, using the Triton WR-1339 method, from 1-2 h after TNF administration there is a 52% increase in total hepatic triglyceride secretion. In contrast, in animals fasted before TNF administration, the characteristic increase in serum triglyceride levels is not observed, and neither the incorporation of glycerol into hepatic lipids nor the quantity of labeled lipids in the circulation are increased. By 17 h after TNF administration the incporation of glycerol into heptic lipid and the quantity of labeled lipid in the serum are no longer increased. These results indicate that in addition to TNF acutely stimulating de novo fatty acid synthesis, TNF also acutely stimulates hepatic triglyceride synthesis. The increase in hepatic triglyceride synthesis leads to increased secretion of lipids into the circulation. These observations provide strong support for our hypothesis that a TNF-induced stimulation of hepatic lipid synthesis and secretion contributes to the TNF-induced hyperlipidemia.