ERRγ Preserves Brown Fat Innate Thermogenic Activity

被引：28

作者：

Ahmadian, Maryam ^{[1
]}

Liu, Sihao ^{[1
]}

Reilly, Shannon M. ^{[2
]}

Hah, Nasun ^{[1
]}

Fan, Weiwei ^{[1
]}

Yoshihara, Eiji ^{[1
]}

Jha, Pooja ^{[3
]}

De Magalhaes Filho, C. Daniel ^{[1
]}

Jacinto, Sandra ^{[1
]}

Gomez, Andrew V. ^{[2
]}

Dai, Yang ^{[1
]}

Yu, Ruth T. ^{[1
]}

Liddle, Christopher ^{[4
,5
]}

Atkins, Annette R. ^{[1
]}

Auwerx, Johan ^{[3
]}

Saltiel, Alan R. ^{[2
]}

Downes, Michael ^{[1
]}

Evans, Ronald M. ^{[1
,6
]}

机构：

[1] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[3] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland

[4] Univ Sydney, Westmead Inst Med Res, Storr Liver Ctr, Westmead, NSW 2145, Australia

[5] Univ Sydney, Sydney Med Sch, Westmead, NSW 2145, Australia

[6] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

来源：

CELL REPORTS | 2018年 / 22卷 / 11期

基金：

英国医学研究理事会; 瑞士国家科学基金会;

关键词：

ADIPOSE-TISSUE; RECEPTOR-ALPHA; ADULT HUMANS; METABOLISM; IDENTIFICATION; TRANSCRIPTION; LOCALIZATION; EXPRESSION; GLUCOSE; WHITE;

D O I：

10.1016/j.celrep.2018.02.061

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Brown adipose tissue (BAT) adaptively transfers energy from glucose and fat into heat by inducing a gene network that uncouples mitochondrial electron transport. However, the innate transcription factors that enable the rapid adaptive response of BAT are unclear. Here, we identify estrogen-related receptor gamma (ERRg) as a critical factor for maintaining BAT identity. ERRg is selectively expressed in BAT versus WAT, in which, in the absence of PGC1a, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i.e., thermoneutral) state. Mice lacking ERRg in adipose tissue(ERRgKOmice) displaymarkeddownregulation of BAT-selective genes that leads to a pronounced whitening of BAT. Consistent with the transcriptional changes, the thermogenic capacity of ERRgKO mice is severely blunted, such that they fail to survive an acute cold challenge. These findings reveal a role for ERRg as a critical thermoneutral maintenance factor required to prime BAT for thermogenesis.

引用

页码：2849 / 2859

页数：11

共 43 条

[1] Desnutrin/ATGL Is Regulated by AMPK and Is Required for a Brown Adipose Phenotype [J].

Ahmadian, Maryam ;

Abbott, Marcia J. ;

Tang, Tianyi ;

Hudak, Carolyn S. S. ;

Kim, Yangha ;

Bruss, Matthew ;

Hellerstein, Marc K. ;

Lee, Hui-Young ;

Samuel, Varman T. ;

Shulman, Gerald I. ;

Wang, Yuhui ;

Duncan, Robin E. ;

Kang, Chulho ;

Sul, Hei Sook .

CELL METABOLISM, 2011, 13 (06) :739-748

[2] ERRγ directs and maintains the transition to oxidative metabolism in the postnatal heart [J].

Alaynick, William A. ;

Kondo, Richard P. ;

Xie, Wen ;

He, Weimin ;

Dufour, Catherine R. ;

Downes, Michael ;

Jonker, Johan W. ;

Giles, Wayne ;

Naviaux, Robert K. ;

Giguere, Vincent ;

Evans, Ronald M. .

CELL METABOLISM, 2007, 6 (01) :13-24

[3] ERRγ Regulates Cardiac, Gastric, and Renal Potassium Homeostasis [J].

Alaynick, William A. ;

Way, James M. ;

Wilson, Stephanie A. ;

Benson, William G. ;

Pei, Liming ;

Downes, Michael ;

Yu, Ruth ;

Jonker, Johan W. ;

Holt, Jason A. ;

Rajpal, Deepak K. ;

Li, Hao ;

Stuart, Joan ;

McPherson, Ruth ;

Remlinger, Katja S. ;

Chang, Ching-Yi ;

McDonnell, Donald P. ;

Evans, Ronald M. ;

Billin, Andrew N. .

MOLECULAR ENDOCRINOLOGY, 2010, 24 (02) :299-309

[4] Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits [J].

Andreux, Penelope A. ;

Williams, Evan G. ;

Koutnikova, Hana ;

Houtkooper, Riekelt H. ;

Champy, Marie-France ;

Henry, Hugues ;

Schoonjans, Kristina ;

Williams, Robert W. ;

Auwerx, Johan .

CELL, 2012, 150 (06) :1287-1299

[5]

Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]

[6] Brown adipose tissue: Function and physiological significance [J].

Cannon, B ;

Nedergaard, J .

PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359

[7] Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue [J].

Cinti, S ;

Frederich, RC ;

Zingaretti, MC ;

DeMatteis, R ;

Flier, JS ;

Lowell, BB .

ENDOCRINOLOGY, 1997, 138 (02) :797-804

[8] The adipose organ at a glance [J].

Cinti, Saverio .

DISEASE MODELS & MECHANISMS, 2012, 5 (05) :588-594

[9] Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat [J].

Cypess, Aaron M. ;

White, Andrew P. ;

Vemochet, Cecile ;

Schulz, Tim J. ;

Xue, Ruidan ;

Sass, Christina A. ;

Huang, Tian Liang ;

Roberts-Toler, Carla ;

Weiner, Lauren S. ;

Sze, Cathy ;

Chacko, Aron T. ;

Deschamps, Laura N. ;

Herder, Lindsay M. ;

Truchan, Nathan ;

Glasgow, Allison L. ;

Holman, Ashley R. ;

Gavrila, Alina ;

Hasselgren, Per-Olof ;

Mori, Marcelo A. ;

Molla, Michael ;

Tseng, Yu-Hua .

NATURE MEDICINE, 2013, 19 (05) :635-639

[10] Identification and Importance of Brown Adipose Tissue in Adult Humans. [J].

Cypess, Aaron M. ;

Lehman, Sanaz ;

Williams, Gethin ;

Tal, Ilan ;

Rodman, Dean ;

Goldfine, Allison B. ;

Kuo, Frank C. ;

Palmer, Edwin L. ;

Tseng, Yu-Hua ;

Doria, Alessandro ;

Kolodny, Gerald M. ;

Kahn, C. Ronald .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (15) :1509-1517

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