Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation

Erin L. Brown, Bethany C. Hazen, Elodie Eury, Jean Sébastien Wattez, Marin L. Gantner, Verena Albert, Sarah Chau, Manuel Sanchez-Alavez, Bruno Conti, Anastasia Kralli

Research output: Contribution to journalArticlepeer-review

Abstract

Adrenergic stimulation of brown adipose tissue (BAT) induces acute and long-term responses. The acute adrenergic response activates thermogenesis by uncoupling oxidative phosphorylation and enabling increased substrate oxidation. Long-term, adrenergic signaling remodels BAT, inducing adaptive transcriptional changes that expand thermogenic capacity. Here, we show that the estrogen-related receptors alpha and gamma (ERRα, ERRγ) are collectively critical effectors of adrenergically stimulated transcriptional reprogramming of BAT. Mice lacking adipose ERRs (ERRαγAd−/−) have reduced oxidative and thermogenic capacity and rapidly become hypothermic when exposed to cold. ERRαγAd−/− mice treated long term with a β3-adrenergic agonist fail to expand oxidative or thermogenic capacity and do not increase energy expenditure in response to norepinephrine (NE). Furthermore, ERRαγAd−/− mice fed a high-fat diet do not lose weight or show improved glucose tolerance when dosed with β3-adrenergic agonists. The molecular basis of these defects is the finding that ERRs mediate the bulk of the transcriptional response to adrenergic stimulation. Adrenergic Receptor Function; Biochemical Mechanism; Molecular Biology

Original languageEnglish (US)
Pages (from-to)221-237
Number of pages17
JournaliScience
Volume2
DOIs
StatePublished - Apr 27 2018

Keywords

  • Adrenergic Receptor Function
  • Biochemical Mechanism
  • Molecular Biology

ASJC Scopus subject areas

  • General

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