Work

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

Year: 2017

Type: preprint

Abstract: 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”). 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. 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 increased glucose sensitivity. 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. Taken together, our findings highlight a therapeutic potential for obese/diabetic postmenopausal patients.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/229591

Authors: Kfir Lapid, Ajin Lim, Eric D. Berglund, Jonathan M. Graff

Institution: The University of Texas Southwestern Medical Center

Language: English

Topic: Adipose Tissue and Metabolism

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: American Heart Association, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases