Impact of perturbed pyruvate metabolism on adipocyte triglyceride accumulation
Impact of perturbed pyruvate metabolism on adipocyte triglyceride accumulation
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DOI：
10.1016/j.ymben.2009.08.001
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发表时间：
2009-11-01
影响因子：
8.4
通讯作者：
Lee, Kyongbum
中科院分区：
文献类型：
--
作者：
Si, Yaguang;Shi, Hai;Lee, Kyongbum
本研究旨在检验脂肪细胞 TG 积累可以通过特异性扰动丙酮酸代谢来改变的假设。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，并使用代谢流和同位素分析来表征它们对中间代谢的整体影响。根据过氧化物酶体增殖物激活受体-g 和甘油-3-磷酸脱氢酶的表达水平评估，抑制这些酶几天不会改变脂肪细胞分化程序。主要代谢作用是上调细胞内脂肪分解并减少TG积累。抑制 PC 还可上调糖酵解。通量估计表明 TG 的减少是由于脂肪酸从头合成的减少。外源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，但在未处理的对照细胞中则没有。这项研究的结果支持了我们关于丙酮酸反应在 TG 合成中的关键作用的假设。 (C) 2009 Elsevier Inc. 保留所有权利。
This study aimed to test the hypo thesis 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-g 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. (C) 2009 Elsevier Inc. All rights reserved.