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 journalArticle

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
JournalFood Science and Human Wellness
Volume2
DOIs
StatePublished - Apr 27 2018

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Brown Adipose Tissue
brown adipose tissue
Estrogen Receptors
Adrenergic Agents
adrenergic agonists
estrogens
Adrenergic Agonists
receptors
mice
biochemical mechanisms
oxidative phosphorylation
adrenergic receptors
glucose tolerance
high fat diet
heat production
norepinephrine
energy expenditure
molecular biology
Thermogenesis
Oxidative Phosphorylation

Keywords

  • Adrenergic Receptor Function
  • Biochemical Mechanism
  • Molecular Biology

ASJC Scopus subject areas

  • Food Science
  • General

Cite this

Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation. / Brown, Erin L.; Hazen, Bethany C.; Eury, Elodie; Wattez, Jean Sébastien; Gantner, Marin L.; Albert, Verena; Chau, Sarah; Sanchez-Alavez, Manuel; Conti, Bruno; Kralli, Anastasia.

In: Food Science and Human Wellness, Vol. 2, 27.04.2018, p. 221-237.

Research output: Contribution to journalArticle

Brown, EL, Hazen, BC, Eury, E, Wattez, JS, Gantner, ML, Albert, V, Chau, S, Sanchez-Alavez, M, Conti, B & Kralli, A 2018, 'Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation', Food Science and Human Wellness, vol. 2, pp. 221-237. https://doi.org/10.1016/j.isci.2018.03.005
Brown, Erin L. ; Hazen, Bethany C. ; Eury, Elodie ; Wattez, Jean Sébastien ; Gantner, Marin L. ; Albert, Verena ; Chau, Sarah ; Sanchez-Alavez, Manuel ; Conti, Bruno ; Kralli, Anastasia. / Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation. In: Food Science and Human Wellness. 2018 ; Vol. 2. pp. 221-237.
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