Boston University School of Medicine, Boston, Massachusetts, USA.
Diabetes. 2010 Apr;59(4):775-81. doi: 10.2337/db09-1602. Epub 2010 Jan 12.
In metazoans, target of rapamycin complex 1 (TORC1) plays the key role in nutrient- and hormone-dependent control of metabolism. However, the role of TORC1 in regulation of triglyceride storage and metabolism remains largely unknown.
In this study, we analyzed the effect of activation and inhibition of the mammalian TORC1 (mTORC1) signaling pathway on the expression of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), lipolysis, lipogenesis, and lipid storage in different mammalian cells.
Activation of mTORC1 signaling in 3T3-L1 adipocytes by ectopic expression of Rheb inhibits expression of ATGL and HSL at the level of transcription, suppresses lipolysis, increases de novo lipogenesis, and promotes intracellular accumulation of triglycerides. Inhibition of mTORC1 signaling by rapamycin or by knockdown of raptor stimulates lipolysis primarily via activation of ATGL expression. Analogous results have been obtained in C2C12 myoblasts and mouse embryonic fibroblasts with genetic ablation of tuberous sclerosis 2 (TSC2) gene. Overexpression of ATGL in these cells antagonized the lipogenic effect of TSC2 knockout.
Our findings demonstrate that mTORC1 promotes fat storage in mammalian cells by suppression of lipolysis and stimulation of de novo lipogenesis.
在后生动物中，雷帕霉素复合物 1（TORC1）在营养和激素依赖性代谢调控中发挥关键作用。然而，TORC1 在调节甘油三酯储存和代谢中的作用在很大程度上仍不清楚。
在本研究中，我们分析了激活和抑制哺乳动物 TORC1（mTORC1）信号通路对不同哺乳动物细胞中脂肪甘油三酯脂肪酶（ATGL）、激素敏感脂肪酶（HSL）、脂肪分解、脂肪生成和脂质储存表达的影响。
在 3T3-L1 脂肪细胞中，通过过表达 Rheb 激活 mTORC1 信号，可在转录水平上抑制 ATGL 和 HSL 的表达，抑制脂肪分解，增加从头脂肪生成，并促进甘油三酯在细胞内的积累。通过 rapamycin 或 Raptor 的敲低抑制 mTORC1 信号，主要通过激活 ATGL 的表达来刺激脂肪分解。在 C2C12 成肌细胞和敲除结节性硬化症 2（TSC2）基因的小鼠胚胎成纤维细胞中也得到了类似的结果。在这些细胞中转染 ATGL 可拮抗 TSC2 缺失的脂肪生成作用。
我们的研究结果表明，mTORC1 通过抑制脂肪分解和刺激从头脂肪生成来促进哺乳动物细胞的脂肪储存。
