Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage.
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.
Chakrabarti
Partha
P
Boston University School of Medicine, Boston, Massachusetts, USA.
English
Taylor
T
Shi
Jun
J
Smas
Cynthia M
CM
Kandror
Konstantin V
KV
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
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