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dc.contributor.authorClookey, S.L.eng
dc.contributor.authorWelly, R.J.eng
dc.contributor.authorShay, D.eng
dc.contributor.authorWoodford, M.L.eng
dc.contributor.authorFritsche, K.L.eng
dc.contributor.authorRector, R.S.eng
dc.contributor.authorPadilla, J.eng
dc.contributor.authorLubahn, D.B.eng
dc.contributor.authorVieira-Potter, V.J.eng
dc.contributor.deptlabNutrition & Exercise Phys-HESeng
dc.date.issued2019eng
dc.description.abstractMetabolic disease risk escalates following menopause. The mechanism is not fully known, but likely involves reduced signaling through estrogen receptor alpha (ER[alpha]), which is highly expressed in brown and white adipose tissue (BAT and WAT). Objective: Test the hypothesis that uncoupling protein (UCP1) activation mitigates metabolic dysfunction caused by loss of signaling through ER[alpha]. Methods: At 8 weeks of age, female ER[alpha] knock out (KO) and wild-type mice were housed at 28∘C and fed a Western-style high-fat, high sucrose diet (HFD) or a normal low-fat chow diet (NC) for 10 weeks. During the final 2 weeks, they received daily injections of CL 316,256 (CL), a selective [beta]3 adrenergic agonist, or vehicle control (CTRL), creating eight groups: WT-CTRL, WT-CL, KO-CTRL, and KO-CL on HFD or NC; n = 4–10/group. Results: ER[alpha]KO demonstrated exacerbated HFD-induced adiposity gain (P < 0.001) and insulin resistance (P = 0.006). CL treatment improved insulin sensitivity (P < 0.05) and normalized ER[alpha]KO-induced adiposity increase (P < 0.05). In both genotypes, CL increased resting energy expenditure (P < 0.05) and induced WAT beiging indicated by increased UCP1 protein in both perigonadal (PGAT) and subcutaneous (SQAT) depots. These effects were attenuated under HFD conditions (P < 0.05). In KO, CL reduced HFD energy consumption compared to CTRL (P < 0.05). Remarkably, CL increased WAT ER[beta] protein levels of both WT and KO (P < 0.001), revealing CL-mediated changes in estrogen signaling may have protective metabolic effects. Conclusion: CL completely restored metabolic dysfunction in ER[alpha]KO mice. Thus, UCP1 may be a therapeutic target for treating metabolic dysfunction following loss of estrogen receptor signaling. Copyrighteng
dc.format.extent15 pages : illustrationeng
dc.identifier10.3389/fphys.2019.00009eng
dc.identifier.urihttps://hdl.handle.net/10355/75235
dc.identifier.urihttps://dx.doi.org/10.3389/fphys.2019.00009eng
dc.languageEnglisheng
dc.publisherFrontiers Media S.A.eng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution 4.0 License.eng
dc.rights.licensehttps://creativecommons.org/licenses/by/4.0eng
dc.sourceFrontiers in Physiologyeng
dc.sourceClookey, S.L., Welly, R.J., Shay, D., Woodford, M.L., Fritsche, K.L., Rector, R.S., Padilla, J., Lubahn, D.B., Vieira-Potter, V.J.. (2019). Beta 3 adrenergic receptor activation rescues metabolic dysfunction in female estrogen receptor alpha-null mice. Frontiers in Physiology, 10(FEB). 10.3389/fphys.2019.00009eng
dc.subject243 ; Adipose tissue ; Browning ; CL 316 ; Energy expenditure ; High fat diet ; Insulin resistance ; Obesity ; Rodenteng
dc.titleBeta 3 adrenergic receptor activation rescues metabolic dysfunction in female estrogen receptor alpha-null miceeng
dc.typeArticleeng


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