Diabetes. 2010 Jan 12. [Epub ahead of print]
The mTOR complex 1 suppresses lipolysis, stimulates lipogenesis and promotes fat storage.
Chakrabarti P, English T, Shi J, Smas CM, Kandror KV.
*Boston University School of Medicine, Boston, MA 02118.
Objective - In metazoans, TOR (target of rapamycin) complex 1 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. Research design and methods - In this study, we analyzed the effect of activation and inhibition of the mTORC1 signaling pathway on the expression of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), lipolysis, lipogenesis, and lipid storage in different mammalian cells. Results - 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 knock down 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 tubero-sclerosis 2 gene (TSC2). Over expression of ATGL in these cells antagonized the lipogenic effect of TSC2 knock out. Conclusions - Our findings demonstrate that mTORC1 promotes fat storage in mammalian cells by suppression of lipolysis and stimulation of de novo lipogenesis.
Hence leucine makes you fat
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