Bile acid excess impairs thermogenic function in brown adipose tissue
Bile acid excess impairs thermogenic function in brown adipose tissue
SUMMARY Bile acids (BAs) not only facilitate fat digestion but also protect against obesity. Here, we show that a genetic mouse model for BA overload (Farnesoid X receptor; Small heterodimer double knockout (DKO)) exhibits mitochondrial dysfunction resulting in a thermogenic defect. By housing DKO mice at thermoneutrality, the poor mitochondrial function in brown fat protects them from diet-induced obesity. Compared to control, we find higher adipose BA levels with excess accumulation of taurocholic acid in the DKO mice. We report that the expression of genes responsible for BA de novo synthesis, conjugation and transporters and accumulation of BAs are present in both brown and white adipocytes. We determine that BA overload is sufficient to cause adipocyte mitochondrial dysfunction and induce the expression of cellular senescence genes in vitro. Taken together, we uncover that BA levels within the adipose tissue may modulate its overall function. HighlightsMouse model of BA overload exhibits adipose defects, which is partially restored by housing at thermoneutrality.BAs are present in detectable concentrations in both BAT and WAT.Adipocytes express genes responsible for de novo synthesis, conjugation and transport of BAs, and accumulate BAs.Pathological accumulation of BAs impairs mitochondrial function leading to thermogenic defect.
Zhang Chi、Teran-Garcia Margarita、Barragan Maribel、Zhou Weinan、VanDuyne Philip、Riessen Ryan、Boppart Stephen A.、Rowitz Blair M.、Anakk Sayeepriyadarshini
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-ChampaignDivision of Nutritional Sciences, University of Illinois at Urbana-Champaign||Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign||Department of Human Development and Family Studies, University of Illinois at Urbana-ChampaignDivision of Nutritional Sciences, University of Illinois at Urbana-ChampaignDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-ChampaignDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-ChampaignDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-ChampaignBeckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign||Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign||Department of Bioengineering, University of Illinois at Urbana-Champaign||Department of Electrical and Computer Engineering, University of Illinois at Urbana-ChampaignDivision of Nutritional Sciences, University of Illinois at Urbana-Champaign||Carle Foundation Hospital||Carle Illinois College of Medicine, University of Illinois at Urbana-ChampaignDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign
基础医学生理学生物化学
Zhang Chi,Teran-Garcia Margarita,Barragan Maribel,Zhou Weinan,VanDuyne Philip,Riessen Ryan,Boppart Stephen A.,Rowitz Blair M.,Anakk Sayeepriyadarshini.Bile acid excess impairs thermogenic function in brown adipose tissue[EB/OL].(2025-03-28)[2025-05-14].https://www.biorxiv.org/content/10.1101/2020.11.24.396895.点此复制
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