ERRγ Preserves Brown Fat Innate Thermogenic Activity

Abstract

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