Pluto Bioinformatics

GSE104285: RNA sequencing of WT and ERRAd-/- brown adipose tissue treated with CL316,243

Bulk RNA sequencing

Adrenergic stimulation of brown adipose tissue (BAT) activates thermogenesis, by uncoupling oxidative phosphorylation and enabling high rates of substrate oxidation. Moreover, adrenergic stimulation signals to the nucleus, inducing gene expression changes that increase BAT thermogenic and oxidative capacity. The purpose of this study was to determine the role of two orphan nuclear receptors, ERR and ERR, in adipose tissue function in response to adrenergic stimulation. Here we identify ERR and ERR as collectively critical effectors of the adrenergic induced transcriptional program in BAT. Mice lacking adipose ERRs (ERRAd-/-) have diminished oxidative and thermogenic capacity, and become rapidly hypothermic when exposed to cold. Notably, the ability of the 3-adrenergic agonist CL316,243 to expand BAT oxidative and thermogenic capacity, increase energy expenditure, promote weight loss, and improve glucose tolerance is lost in ERRAd-/-. At the transcriptional level, RNA sequencing experiments show that the bulk of the response of BAT to CL316,243 (>80% of CL316,243-induced genes) relies on ERRs. These findings establish ERR and ERR as essential BAT regulators that act coordinately to relay adrenergic signals and expand the capacity for thermogenesis and energy expenditure. SOURCE: Anastasia Kralli ( - Johns Hopkins University

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