title: SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL.
abstract: Recent studies have established SIRT1 as an important regulator of lipid metabolism, although the mechanism of its action at the molecular level has not been revealed. Here, we show that knockdown of SIRT1 with the help of small hairpin RNA decreases basal and isoproterenol-stimulated lipolysis in cultured adipocytes. This effect is attributed, at least in part, to the suppression of the rate-limiting lipolytic enzyme, adipose triglyceride lipase (ATGL), at the level of transcription. Mechanistically, SIRT1 controls acetylation status and functional activity of FoxO1 that directly binds to the ATGL promoter and regulates ATGL gene transcription. We have also found that depletion of SIRT1 decreases AMP-dependent protein kinase (AMPK) activity in adipocytes. To determine the input of AMPK in regulation of lipolysis, we have established a stable adipose cell line that expresses a dominant-negative α1 catalytic subunit of AMPK under the control of the inducible TET-OFF lentiviral expression vector. Reduction of AMPK activity does not have a significant effect on the rates of lipolysis in this cell model. We conclude, therefore, that SIRT1 controls ATGL transcription primarily by deacetylating FoxO1.
authors: Boston University School of Medicine, Boston, MA 02118, USA.
authors: Partha
authors: P
authors: Chakrabarti
authors: Taylor
authors: T
authors: English
authors: Shakun
authors: S
authors: Karki
authors: Li
authors: L
authors: Qiang
authors: Rong
authors: R
authors: Tao
authors: Juyoun
authors: J
authors: Kim
authors: Zhijun
authors: Z
authors: Luo
authors: Stephen R
authors: SR
authors: Farmer
authors: Konstantin V
authors: KV
authors: Kandror
mesh_terms: D041721:3T3-L1 Cells; D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D000818:Animals; D015536:Down-Regulation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008066:Lipolysis / Q000502:physiology*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D000263:Adenylate Kinase; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D008049:Lipase; D047495:PPAR gamma; D034741:RNA, Small Interfering; D056564:Sirtuin 1; C467200:Foxo1 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases; C470545:Sirt1 protein, mouse