title: Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  Our findings demonstrate that mTORC1 promotes fat storage in mammalian cells by suppression of lipolysis and stimulation of de novo lipogenesis.
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Partha
authors.initials: P
authors.lastname: Chakrabarti
authors.forename: Taylor
authors.initials: T
authors.lastname: English
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Smas
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Kandror
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000273:Adipose Tissue / Q000033:anatomy & histology*; D000818:Animals; D001391:Azo Compounds; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000201:enzymology / Q000502:physiology; D017930:Genes, Reporter; D008049:Lipase / Q000235:genetics; D008066:Lipolysis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010101:Oxygen Consumption; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics
chemical_list: D001391:Azo Compounds; C519509:Crtc1 protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014280:Triglycerides; C000624654:Tsc2 protein, mouse; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D012313:RNA; D008049:Lipase; C011049:oil red O