Brown Remodeling of White Adipose Tissue by SirT1-Dependent Deacetylation of Pparγ

被引：723

作者：

Qiang, Li ^{[1
]}

Wang, Liheng ^{[1
]}

Kon, Ning ^{[2
]}

Zhao, Wenhui ^{[2
]}

Lee, Sangkyu ^{[4
]}

Zhang, Yiying ^{[3
]}

Rosenbaum, Michael ^{[3
]}

Zhao, Yingming ^{[4
]}

Gu, Wei ^{[2
]}

Farmer, Stephen R. ^{[5
]}

Accili, Domenico ^{[1
]}

机构：

[1] Columbia Univ, Dept Med, Naomi Berrie Diabet Ctr, Coll Phys & Surg, New York, NY 10032 USA

[2] Columbia Univ, Dept Pathol, Inst Canc Genet, Coll Phys & Surg, New York, NY 10032 USA

[3] Columbia Univ, Coll Phys & Surg, Dept Pediat, Div Mol Genet, New York, NY 10032 USA

[4] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA

[5] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA

来源：

CELL | 2012年 / 150卷 / 03期

关键词：

ACTIVATED-RECEPTOR-GAMMA; INSULIN-RESISTANCE; SIRT1; FAT; PGC-1-ALPHA; METABOLISM; ADIPOCYTES; OBESITY; MICE; THERMOGENESIS;

D O I：

10.1016/j.cell.2012.06.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive, therapeutic approach to staunch the current obesity epidemic. Here we report that gain of function of the NAD-dependent deacetylase SirT1 or loss of function of its endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote "browning" of WAT by deacetylating peroxisome proliferator-activated receptor (Ppar)-gamma on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Ppar gamma, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Pparg mutant induces a brown phenotype in white adipocytes, whereas an acetylated mimetic fails to induce "brown" genes but retains the ability to activate "white" genes. We propose that SirT1-dependent Pparg deacetylation is a form of selective Ppar gamma modulation of potential therapeutic import.

引用

页码：620 / 632

页数：13

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