ERR? Preserves Brown Fat Innate Thermogenic Activity.

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 (ERR?) as a critical factor for maintaining BAT identity. ERR? is selectively expressed in BAT versus WAT, in which, in the absence of PGC1?, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i.e., thermoneutral) state. Mice lacking ERR? in adipose tissue (ERR?KO 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 ERR?KO mice is severely blunted, such that they fail to survive an acute cold challenge. These findings reveal a role for ERR? as a critical thermoneutral maintenance factor required to prime BAT for thermogenesis.

SUBMITTER: Ahmadian M 

PROVIDER: S-EPMC5884669 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature