Mammalian Target of Rapamycin Complex 1 Suppresses Lipolysis, Stimulates Lipogenesis, and Promotes Fat Storage

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 4; pp. 775 - 781
• Main Authors: CHAKRABARTI, Partha, ENGLISH, Taylor, JUN SHI, SMAS, Cynthia M, KANDROR, Konstantin V
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2010
• Subjects: 3T3 Cells; Ablation; Adipocytes; Adipocytes - cytology; Adipocytes - physiology; Adipose Tissue - anatomy & histology; Animals; Autophagy; Azo Compounds; Base Sequence; Biological and medical sciences; Cell Differentiation; Cells, Cultured - enzymology; Cells, Cultured - physiology; Development and progression; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy; Enzymes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fibroblasts; Genes, Reporter; Hamartoma; Health aspects; Kidney diseases; Kinases; Lipase - genetics; Lipolysis; Lipolysis - physiology; Mammals; Medical sciences; Metabolism; Mice; Mice, Knockout; Original; Oxygen Consumption; Physiological aspects; Polyclonal antibodies; Polymerase Chain Reaction; Protein kinases; Proteins; Research design; Risk factors; RNA - genetics; RNA - isolation & purification; RNA, Small Interfering - genetics; Transcription Factors - genetics; Transcription Factors - physiology; Transfection; Triglycerides - metabolism; Tumor Suppressor Proteins - deficiency; Tumor Suppressor Proteins - genetics; United States; Endocrinopathy; Vertebrata; Mammalia; Storage; Diabetes mellitus; Lipogenesis; Lipolysis
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db09-1602

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.