SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation

被引：431
作者：
Jing, Enxuan [1 ]
Gesta, Stephane [1 ]
Kahn, C. Ronald [1 ]
机构：
[1] Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02215 USA
来源：
CELL METABOLISM | 2007年 / 6卷 / 02期
关键词：
D O I：
10.1016/j.cmet.2007.07.003
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The family of mammalian Sirtuin proteins comprises seven members homologous to yeast Sir2. Here we show that SIRT2, a cytoplasmic sirtuin, is the most abundant sirtuin in adipocytes. Sirt2 expression is downregulated during preadipocyte differentiation in 3T3-L1 cells. Overexpression of SIRT2 inhibits differentiation, whereas reducing SIRT2 expression promotes adipogenesis. Both effects are accompanied by corresponding changes in the expression of PPAR gamma, C/EBP alpha, and genes marking terminal adipocyte differentiation, including Glut4, aP2, and fatty acid synthase. The mechanism underlying the effects of reduced SIRT2 in 3T3-L1 adipocytes includes increased acetylation of FOXO1, with direct interaction between SIRT2 and FOXO1. This interaction enhances insulin-stimulated phosphorylation of FOXO1, which in turn regulates FOXO1 nuclear and cytosolic localization. Thus, Sirt2 acts as an important regulator of adipocyte differentiation through modulation of FOXO1 acetylation/phosphorylation and activity and may play a role in controlling adipose tissue mass and function.
引用
收藏
页码：105 / 114
页数：10
相关论文
共 42 条
[1]   FOXO1 represses peroxisome proliferator-activated receptor-γ1 and -γ2 gene promoters in primary adipocytes -: A novel paradigm to increase insulin sensitivity [J].
Armoni, Michal ;
Harel, Chava ;
Karni, Shiri ;
Chen, Hui ;
Bar-Yoseph, Fabiana ;
Ver, Marel R. ;
Quon, Michael J. ;
Karnieli, Eddy .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (29) :19881-19891
[2]   FoxO proteins in insulin action and metabolism [J].
Barthel, A ;
Schmoll, D ;
Unterman, TG .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2005, 16 (04) :183-189
[3]   Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity [J].
Daitoku, H ;
Hatta, M ;
Matsuzaki, H ;
Aratani, S ;
Ohshima, T ;
Miyagishi, M ;
Nakajima, T ;
Fukamizu, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (27) :10042-10047
[4]   Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle [J].
Dryden, SC ;
Nahhas, FA ;
Nowak, JE ;
Goustin, AS ;
Tainsky, MA .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (09) :3173-3185
[5]   SOCS-3 is an insulin-induced negative regulator of insulin signaling [J].
Emanuelli, B ;
Peraldi, P ;
Filloux, C ;
Sawka-Verhelle, D ;
Hilton, D ;
Van Obberghen, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (21) :15985-15991
[6]   RETRACTED: Bi-directional regulation of brown fat adipogenesis by the insulin receptor (Retracted article. See vol. 291, pg. 27434, 2016) [J].
Entingh, AJ ;
Taniguchi, CM ;
Kahn, CR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) :33377-33383
[7]   Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity [J].
Feng, LJ ;
Lin, TX ;
Uranishi, H ;
Gu, W ;
Xu, Y .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (13) :5389-5395
[8]   Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription [J].
Ford, E ;
Voit, R ;
Liszt, G ;
Magin, C ;
GrumMt, I ;
Guarente, L .
GENES & DEVELOPMENT, 2006, 20 (09) :1075-1080
[9]   Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes [J].
Frescas, D ;
Valenti, L ;
Accili, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (21) :20589-20595
[10]   Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state [J].
Fulco, M ;
Schiltz, RL ;
Iezzi, S ;
King, MT ;
Zhao, P ;
Kashiwaya, Y ;
Hoffman, E ;
Veech, RL ;
Sartorelli, V .
MOLECULAR CELL, 2003, 12 (01) :51-62
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