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Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
Journal article   Open access   Peer reviewed

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

Kfir Lapid, Ajin Lim, Eric D. Berglund and Yue Lu
Diabetes, metabolic syndrome and obesity, Vol.12, pp.1419-1436
08/01/2019
DOI: 10.2147/DMSO.S190752
PMCID: PMC6699149
PMID: 31616172
url
https://doi.org/10.2147/DMSO.S190752View
Published (Version of record) Open Access

Abstract

Background: 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 (ER alpha) 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 ER alpha 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 - ER alpha KO mice, ovariectomy, and treatment with the ER alpha antagonist Fulvestrant - supported this notion. ER alpha/estrogen-deficient mice demonstrated enhanced cold-induced beiging, reduced adiposity and improved glucose tolerance. Fulvestrant was also effective in diet-induced obesity settings. Mechanistically, ER alpha inhibition sensitized cell-autonomous beige cell differentiation and stimulation, including beta 3-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.
 Endocrinology & Metabolism Life Sciences & Biomedicine Science & Technology

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