ERRγ Preserves Brown Fat Innate Thermogenic Activity
Maryam Ahmadian,
Sihao Liu,
Shannon M. Reilly,
Nasun Hah,
Weiwei Fan,
Eiji Yoshihara,
Pooja Jha,
C. Daniel De Magalhaes Filho,
Sandra Jacinto,
Andrew V. Gomez,
Yang Dai,
Ruth T. Yu,
Christopher Liddle,
Annette R. Atkins,
Johan Auwerx,
Alan R. Saltiel,
Michael Downes,
Ronald M. Evans
Affiliations
Maryam Ahmadian
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Sihao Liu
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Shannon M. Reilly
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0757, USA
Nasun Hah
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Weiwei Fan
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Eiji Yoshihara
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Pooja Jha
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
C. Daniel De Magalhaes Filho
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Sandra Jacinto
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Andrew V. Gomez
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0757, USA
Yang Dai
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Ruth T. Yu
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Christopher Liddle
Storr Liver Centre, The Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia
Annette R. Atkins
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Johan Auwerx
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
Alan R. Saltiel
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0757, USA
Michael Downes
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Corresponding author
Ronald M. Evans
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; Corresponding author
Summary: 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. : Ahmadian et al. find that estrogen-related receptor gamma (ERRγ) is a critical factor for maintaining brown fat identity. They find that ERRγ controls a transcriptional network of thermogenic genes in the basal state. Mice lacking ERRγ exhibit a whitening of brown fat and are unable to survive an acute cold challenge. Keywords: estrogen related receptor gamma, brown fat, thermogenesis, thermoneutrality, BAT, brown adipocyte
