The exercise-inducible bile acid receptor Tgr5 improves skeletal muscle function in mice

The Journal of Biological Chemistry
Takashi SasakiRyuichiro Sato

Abstract

TGR5 (also known as G protein-coupled bile acid receptor 1, GPBAR1) is a G protein-coupled bile acid receptor that is expressed in many diverse tissues. TGR5 is involved in various metabolic processes, including glucose metabolism and energy expenditure; however, TGR5's function in skeletal muscle is not fully understood. Using both gain- and loss-of-function mouse models, we demonstrate here that Tgr5 activation promotes muscle cell differentiation and muscle hypertrophy. Both young and old transgenic mice with muscle-specific Tgr5 expression exhibited increased muscle strength. Moreover, we found that Tgr5 expression is increased by the unfolded protein response (UPR), which is an adaptive response required for maintenance of endoplasmic reticulum (ER) homeostasis. Both ER stress response element (ERSE)- and unfolded protein response element (UPRE)-like sites are present in the 5' upstream region of the Tgr5 gene promoter and are essential for Tgr5 expression by Atf6α (activating transcription factor 6α), a well known UPR-activated transcriptional regulator. We observed that in the skeletal muscle of mice, exercise-induced UPR increases Tgr5 expression, an effect that was abrogated in Atf6α KO mice, indicating that Atf6α is e...Continue Reading

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Citations

Feb 18, 2020·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Gizem GemikonakliSarah Nicole Hilmer
Aug 14, 2020·Physiological Reviews·Alessia PerinoKristina Schoonjans
Aug 20, 2020·Expert Review of Gastroenterology & Hepatology·Tiziana Fernández-MinconeFrancisco Barrera
Jun 9, 2020·Journal of Cellular Physiology·Johanna AbrigoClaudio Cabello-Verrugio
Jul 28, 2020·Nutrients·Marlena M HolterBethany P Cummings
Jul 14, 2020·Bioscience, Biotechnology, and Biochemistry·Ryuichiro Sato
Jul 30, 2020·International Journal of Molecular Sciences·Hiroki NishikawaHiroko Iijima
Nov 10, 2020·Biological Reviews of the Cambridge Philosophical Society·Kang Nian YapWendy R Hood
Dec 3, 2020·The Journal of Biological Chemistry·Takashi SasakiRyuichiro Sato
Oct 30, 2020·International Journal of Molecular Sciences·Johanna AbrigoClaudio Cabello-Verrugio
Jan 19, 2021·The Journal of Biological Chemistry·Takashi SasakiRyuichiro Sato
Aug 31, 2021·Bioscience, Biotechnology, and Biochemistry·Shotaro MurataRyuichiro Sato
Sep 28, 2021·The Journal of Physiology·Taylor R ValentinoJohn J McCarthy
Nov 1, 2021·The Journal of Clinical Endocrinology and Metabolism·Francisco J Osuna-PrietoBorja Martinez-Tellez

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