Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance

Kfir Lapid,1,2 Ajin Lim,1 Eric D Berglund,3,4 Yue Lu21Department of Developmental Biology; 2Division of Endocrinology, Department of Internal Medicine; 3Advanced Imaging Research Center; 4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USABackground:&nbsp...

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Autores principales:	Lapid K, Lim A, Berglund ED, Lu Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Adipose tissue post-menopause brown fat obesity diabetes Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/9f0d650a27f3416cb2c4c286830004e9
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spelling	oai:doaj.org-article:9f0d650a27f3416cb2c4c286830004e92021-12-02T10:48:27ZEstrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance1178-7007https://doaj.org/article/9f0d650a27f3416cb2c4c286830004e92019-08-01T00:00:00Zhttps://www.dovepress.com/estrogen-receptor-inhibition-enhances-cold-induced-adipocyte-beiging-a-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Kfir Lapid,1,2 Ajin Lim,1 Eric D Berglund,3,4 Yue Lu21Department of Developmental Biology; 2Division of Endocrinology, Department of Internal Medicine; 3Advanced Imaging Research Center; 4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USABackground: Low estrogen states, exemplified by postmenopausal women, are associated with increased adiposity and metabolic dysfunction. We recently reported a paradox, in which a conditional estrogen receptor-alpha (ERα) mutant mouse shows a hyper-metabolic phenotype with enhanced brown/beige cell formation (“browning/beiging”).Hypothesis: These observations led us to consider that although systemic deficiency of estrogen or ERα in mice results in obesity and glucose intolerance at room temperature, cold exposure might induce enhanced browning/beiging and improve glucose metabolism.Methods and results: Remarkably, studying cold-exposure in mouse models of inhibited estrogen signaling - ERαKO mice, ovariectomy, and treatment with the ERα antagonist Fulvestrant - supported this notion. ERα/estrogen-deficient mice demonstrated enhanced cold-induced beiging, reduced adiposity and improved glucose tolerance. Fulvestrant was also effective in diet-induced obesity settings. Mechanistically, ERα inhibition sensitized cell-autonomous beige cell differentiation and stimulation, including β3-adrenoreceptor-dependent adipocyte beiging.Conclusion: Taken together, our findings highlight a therapeutic potential for obese/diabetic postmenopausal patients; cold exposure is therefore predicted to metabolically benefit those patients.Keywords: adipose tissue, post-menopause, brown fat, obesity, diabetesLapid KLim ABerglund EDLu YDove Medical PressarticleAdipose tissuepost-menopausebrown fatobesitydiabetesSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 1419-1436 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Adipose tissue post-menopause brown fat obesity diabetes Specialties of internal medicine RC581-951
spellingShingle	Adipose tissue post-menopause brown fat obesity diabetes Specialties of internal medicine RC581-951 Lapid K Lim A Berglund ED Lu Y Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
description	Kfir Lapid,1,2 Ajin Lim,1 Eric D Berglund,3,4 Yue Lu21Department of Developmental Biology; 2Division of Endocrinology, Department of Internal Medicine; 3Advanced Imaging Research Center; 4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USABackground: Low estrogen states, exemplified by postmenopausal women, are associated with increased adiposity and metabolic dysfunction. We recently reported a paradox, in which a conditional estrogen receptor-alpha (ERα) mutant mouse shows a hyper-metabolic phenotype with enhanced brown/beige cell formation (“browning/beiging”).Hypothesis: These observations led us to consider that although systemic deficiency of estrogen or ERα in mice results in obesity and glucose intolerance at room temperature, cold exposure might induce enhanced browning/beiging and improve glucose metabolism.Methods and results: Remarkably, studying cold-exposure in mouse models of inhibited estrogen signaling - ERαKO mice, ovariectomy, and treatment with the ERα antagonist Fulvestrant - supported this notion. ERα/estrogen-deficient mice demonstrated enhanced cold-induced beiging, reduced adiposity and improved glucose tolerance. Fulvestrant was also effective in diet-induced obesity settings. Mechanistically, ERα inhibition sensitized cell-autonomous beige cell differentiation and stimulation, including β3-adrenoreceptor-dependent adipocyte beiging.Conclusion: Taken together, our findings highlight a therapeutic potential for obese/diabetic postmenopausal patients; cold exposure is therefore predicted to metabolically benefit those patients.Keywords: adipose tissue, post-menopause, brown fat, obesity, diabetes
format	article
author	Lapid K Lim A Berglund ED Lu Y
author_facet	Lapid K Lim A Berglund ED Lu Y
author_sort	Lapid K
title	Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
title_short	Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
title_full	Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
title_fullStr	Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
title_full_unstemmed	Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
title_sort	estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/9f0d650a27f3416cb2c4c286830004e9
work_keys_str_mv	AT lapidk estrogenreceptorinhibitionenhancescoldinducedadipocytebeigingandglucosetolerance AT lima estrogenreceptorinhibitionenhancescoldinducedadipocytebeigingandglucosetolerance AT berglunded estrogenreceptorinhibitionenhancescoldinducedadipocytebeigingandglucosetolerance AT luy estrogenreceptorinhibitionenhancescoldinducedadipocytebeigingandglucosetolerance
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Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance

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