@article{bb284bbb803d4cefbde89620a9d7c41f,
title = "Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation",
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.",
keywords = "Adrenergic Receptor Function, Biochemical Mechanism, Molecular Biology",
author = "Brown, {Erin L.} and Hazen, {Bethany C.} and Elodie Eury and Wattez, {Jean S{\'e}bastien} and Gantner, {Marin L.} and Verena Albert and Sarah Chau and Manuel Sanchez-Alavez and Bruno Conti and Anastasia Kralli",
note = "Funding Information: We thank Dr. Johan Auwerx for providing the ERR floxed mouse strains; Dr. Malcolm Parker at the TSRI Microscopy core for the EM analyses; Yoshitake Cho, Enrique Saez, Bernard Kok, and other Saez laboratory members for discussions and advice. The study was supported by the National Institute of Health grant R01DK095686 (to A.K.), GM113894 (to B.C.), and the AHA post-doctoral award 16POST31350029 (to E.L.B.). Funding Information: We thank Dr. Johan Auwerx for providing the ERR floxed mouse strains; Dr. Malcolm Parker at the TSRI Microscopy core for the EM analyses; Yoshitake Cho, Enrique Saez, Bernard Kok, and other Saez laboratory members for discussions and advice. The study was supported by the National Institute of Health grant R01DK095686 (to A.K.), GM113894 (to B.C.), and the AHA post-doctoral award 16POST31350029 (to E.L.B.). Conceptualization, E.L.B. and A.K.; Methodology, E.L.B and A.K.; Investigation, E.L.B. B.C.H. E.E. J.-S.W. M.L.G. S.C. M.S.-A. and V.A.; Writing – Original draft, E.L.B. and A.K.; Writing – Review and Editing, E.L.B. B.C.H. E.E. J.-S.W. M.L.G. V.A. M.S.-A. B.C. and A.K.; Supervision, E.L.B. and A.K.; Funding Acquisition, E.L.B. and A.K.; Resources, B.C. and M.S.-A. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = apr,
day = "27",
doi = "10.1016/j.isci.2018.03.005",
language = "English (US)",
volume = "2",
pages = "221--237",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
}