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Cell Rep. 2018 Mar 13;22(11):2849-2859. doi: 10.1016/j.celrep.2018.02.061.

ERRγ Preserves Brown Fat Innate Thermogenic Activity.

Author information

1
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0757, USA.
3
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
4
Storr Liver Centre, The Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia.
5
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: downes@salk.edu.
6
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu.

Abstract

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 (ERRγ) as a critical factor for maintaining BAT identity. ERRγ is selectively expressed in BAT versus WAT, in which, in the absence of PGC1α, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i.e., thermoneutral) state. Mice lacking ERRγ in adipose tissue (ERRγKO mice) display marked downregulation of BAT-selective genes that leads to a pronounced whitening of BAT. Consistent with the transcriptional changes, the thermogenic capacity of ERRγKO mice is severely blunted, such that they fail to survive an acute cold challenge. These findings reveal a role for ERRγ as a critical thermoneutral maintenance factor required to prime BAT for thermogenesis.

KEYWORDS:

BAT; brown adipocyte; brown fat; estrogen related receptor gamma; thermogenesis; thermoneutrality

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