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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Aug 7

PMID 22863012

Citations 413

Authors

Li Qiang

Liheng Wang

Ning Kon

Wenhui Zhao

Sangkyu Lee

Yiying Zhang

Michael Rosenbaum

Yingming Zhao

Wei Gu

Stephen R Farmer

Domenico Accili

Affiliations

Soon will be listed here.

Abstract

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)-γ on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Pparγ, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Pparγ 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 Pparγ deacetylation is a form of selective Pparγ modulation of potential therapeutic import.

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