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SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma.
Mol Biol Cell. 2009 Feb; 20(3):801-8.MB

Abstract

Sirtuin family of proteins possesses NAD-dependent deacetylase and ADP ribosyltransferase activities. They are found to respond to nutrient deprivation and profoundly regulate metabolic functions. We have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue. Because adipose tissue is a key metabolic organ playing a critical role in whole body energy homeostasis, we went on to explore the function of SIRT2 in adipose tissue. We found short-term food deprivation for 24 h, already induces SIRT2 expression in white and brown adipose tissues. Additionally, cold exposure elevates SIRT2 expression in brown adipose tissue but not in white adipose tissue. Intraperitoneal injection of a beta-adrenergic agonist (isoproterenol) enhances SIRT2 expression in white adipose tissue. Retroviral expression of SIRT2 in 3T3-L1 adipocytes promotes lipolysis. SIRT2 inhibits 3T3-L1 adipocyte differentiation in low-glucose (1 g/l) or low-insulin (100 nM) condition. Mechanistically, SIRT2 suppresses adipogenesis by deacetylating FOXO1 to promote FOXO1's binding to PPARgamma and subsequent repression on PPARgamma transcriptional activity. Overall, our results indicate that SIRT2 responds to nutrient deprivation and energy expenditure to maintain energy homeostasis by promoting lipolysis and inhibiting adipocyte differentiation.

Authors+Show Affiliations

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19037106

Citation

Wang, Fei, and Qiang Tong. "SIRT2 Suppresses Adipocyte Differentiation By Deacetylating FOXO1 and Enhancing FOXO1's Repressive Interaction With PPARgamma." Molecular Biology of the Cell, vol. 20, no. 3, 2009, pp. 801-8.
Wang F, Tong Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. Mol Biol Cell. 2009;20(3):801-8.
Wang, F., & Tong, Q. (2009). SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. Molecular Biology of the Cell, 20(3), 801-8. https://doi.org/10.1091/mbc.E08-06-0647
Wang F, Tong Q. SIRT2 Suppresses Adipocyte Differentiation By Deacetylating FOXO1 and Enhancing FOXO1's Repressive Interaction With PPARgamma. Mol Biol Cell. 2009;20(3):801-8. PubMed PMID: 19037106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. AU - Wang,Fei, AU - Tong,Qiang, Y1 - 2008/11/26/ PY - 2008/11/28/pubmed PY - 2009/4/11/medline PY - 2008/11/28/entrez SP - 801 EP - 8 JF - Molecular biology of the cell JO - Mol Biol Cell VL - 20 IS - 3 N2 - Sirtuin family of proteins possesses NAD-dependent deacetylase and ADP ribosyltransferase activities. They are found to respond to nutrient deprivation and profoundly regulate metabolic functions. We have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue. Because adipose tissue is a key metabolic organ playing a critical role in whole body energy homeostasis, we went on to explore the function of SIRT2 in adipose tissue. We found short-term food deprivation for 24 h, already induces SIRT2 expression in white and brown adipose tissues. Additionally, cold exposure elevates SIRT2 expression in brown adipose tissue but not in white adipose tissue. Intraperitoneal injection of a beta-adrenergic agonist (isoproterenol) enhances SIRT2 expression in white adipose tissue. Retroviral expression of SIRT2 in 3T3-L1 adipocytes promotes lipolysis. SIRT2 inhibits 3T3-L1 adipocyte differentiation in low-glucose (1 g/l) or low-insulin (100 nM) condition. Mechanistically, SIRT2 suppresses adipogenesis by deacetylating FOXO1 to promote FOXO1's binding to PPARgamma and subsequent repression on PPARgamma transcriptional activity. Overall, our results indicate that SIRT2 responds to nutrient deprivation and energy expenditure to maintain energy homeostasis by promoting lipolysis and inhibiting adipocyte differentiation. SN - 1939-4586 UR - https://www.unboundmedicine.com/medline/citation/19037106/SIRT2_suppresses_adipocyte_differentiation_by_deacetylating_FOXO1_and_enhancing_FOXO1's_repressive_interaction_with_PPARgamma_ L2 - https://www.molbiolcell.org/doi/10.1091/mbc.e08-06-0647?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -