丙酮酸代谢紊乱对脂肪细胞甘油三酯积累的影响。
Impact of perturbed pyruvate metabolism on adipocyte triglyceride accumulation.
机构信息
Department of Biology, Tufts University, Medford, MA 02155, USA.
出版信息
Metab Eng. 2009 Nov;11(6):382-90. doi: 10.1016/j.ymben.2009.08.001. Epub 2009 Aug 14.
Abstract
This study aimed to test the hypothesis that adipocyte TG accumulation could be altered by specifically perturbing pyruvate metabolism. We treated cultured 3T3-L1 adipocytes with chemical inhibitors of lactate dehydrogenase (LDH) and pyruvate carboxylase (PC), and characterized their global effects on intermediary metabolism using metabolic flux and isotopomer analysis. Inhibiting the enzymes over several days did not alter the adipocyte differentiation program as assessed by the expression levels of peroxisome proliferator-activated receptor-gamma and glycerol-3-phosphate dehydrogenase. The main metabolic effects were to up-regulate intracellular lipolysis and decrease TG accumulation. Inhibiting PC also up-regulated glycolysis. Flux estimates indicated that the reduction in TG was due to decreased de novo fatty acid synthesis. Exogenous addition of free fatty acids dose-dependently increased the cellular TG level in the inhibitor-treated adipocytes, but not in untreated control cells. The results of this study support our hypothesis regarding the critical role of pyruvate reactions in TG synthesis.
摘要
本研究旨在验证一个假设，即通过特异性干扰丙酮酸代谢可以改变脂肪细胞 TG 的积累。我们用乳酸脱氢酶 (LDH) 和丙酮酸羧化酶 (PC) 的化学抑制剂处理培养的 3T3-L1 脂肪细胞，并使用代谢通量和同位素分析方法来描述它们对中间代谢的全局影响。在几天的时间里，抑制这些酶的活性不会改变过氧化物酶体增殖物激活受体-γ和甘油-3-磷酸脱氢酶的表达水平，从而评估脂肪细胞的分化程序。主要的代谢效应是上调细胞内脂解作用并减少 TG 积累。抑制 PC 还会上调糖酵解。通量估计表明，TG 的减少是由于从头脂肪酸合成减少所致。外源性添加游离脂肪酸剂量依赖性地增加了抑制剂处理的脂肪细胞中的细胞 TG 水平，但未处理的对照细胞中则没有增加。本研究的结果支持我们关于丙酮酸反应在 TG 合成中起关键作用的假设。
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