Lectures and seminars Guest seminar: Professor Steven Kliewer
Wednesday November 19 at 3pm in room Nils Ringertz, Biomedicum. Title: “Battling the Bottle: Discovery of a Hormone Ally Against Alcohol”.
Welcome to a guest seminar by Steven Kliewer
Professor of Molecular Biology and Pharmacology at the University of Texas Southwestern Medical Center, USA
Dr. Steven Kliewer research focuses on the roles of nuclear receptors and endocrine FGFs in regulating diverse aspects of physiology and pathophysiology, including metabolism and related diseases. Among his ongoing projects, he is studying how FGF19 and FGF21 regulate bile acid and energy homeostasis, respectively, and how the dafachronic acid receptor, DAF-12, regulates the infectious lifecycle of parasitic nematodes.
Abstract
Fibroblast growth factor 21 (FGF21) is an unusual member of the FGF family that can circulate in the blood as a hormone. FGF21 is strongly induced by ethanol in both human and rodent liver, and human GWAS studies have associated genetic variants in FGF21 and its co-receptor, beta-Klotho, with alcohol consumption. We have shown that in mice, FGF21 acts directly on the nervous system to suppress ethanol preference, stimulate water consumption, and accelerate recovery from intoxication. These findings reveal a broad role for FGF21 in protecting against the harmful effects of ethanol and suggest that it may be useful therapeutically for treating alcohol use disorders.
Selected publications
FGF21 Regulates Sweet and Alcohol Preference.
Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA
Cell Metab 2016 Feb;23(2):344-9
KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.
Schumann G, Liu C, O'Reilly P, Gao H, Song P, Xu B, Ruggeri B, Amin N, Jia T, Preis S, Segura Lepe M, Akira S, Barbieri C, Baumeister S, Cauchi S, Clarke TK, Enroth S, Fischer K, Hällfors J, Harris SE, Hieber S, Hofer E, Hottenga JJ, Johansson Å, Joshi PK, Kaartinen N, Laitinen J, Lemaitre R, Loukola A, Luan J, Lyytikäinen LP, Mangino M, Manichaikul A, Mbarek H, Milaneschi Y, Moayyeri A, Mukamal K, Nelson C, Nettleton J, Partinen E, Rawal R, Robino A, Rose L, Sala C, Satoh T, Schmidt R, Schraut K, Scott R, Smith AV, Starr JM, Teumer A, Trompet S, Uitterlinden AG, Venturini C, Vergnaud AC, Verweij N, Vitart V, Vuckovic D, Wedenoja J, Yengo L, Yu B, Zhang W, Zhao JH, Boomsma DI, Chambers J, Chasman DI, Daniela T, de Geus E, Deary I, Eriksson JG, Esko T, Eulenburg V, Franco OH, Froguel P, Gieger C, Grabe HJ, Gudnason V, Gyllensten U, Harris TB, Hartikainen AL, Heath AC, Hocking L, Hofman A, Huth C, Jarvelin MR, Jukema JW, Kaprio J, Kooner JS, Kutalik Z, Lahti J, Langenberg C, Lehtimäki T, Liu Y, Madden PA, Martin N, Morrison A, Penninx B, Pirastu N, Psaty B, Raitakari O, Ridker P, Rose R, Rotter JI, Samani NJ, Schmidt H, Spector TD, Stott D, Strachan D, Tzoulaki I, van der Harst P, van Duijn CM, Marques-Vidal P, Vollenweider P, Wareham NJ, Whitfield JB, Wilson J, Wolffenbuttel B, Bakalkin G, Evangelou E, Liu Y, Rice KM, Desrivières S, Kliewer SA, Mangelsdorf DJ, Müller CP, Levy D, Elliott P
Proc Natl Acad Sci U S A 2016 Dec;113(50):14372-14377
FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system.
Choi M, Schneeberger M, Fan W, Bugde A, Gautron L, Vale K, Hammer RE, Zhang Y, Friedman JM, Mangelsdorf DJ, Kliewer SA
Cell Metab 2023 Mar;35(3):429-437.e5
Ethanol induction of FGF21 in the liver is dependent on histone acetylation and ligand activation of ChREBP by glycerol-3-phosphate.
Cheong MC, Mackowiak B, Kim HB, Hernandez G, Nandu T, Vale K, Zhang Y, Zacharias LG, Mathews TP, Gao B, Kraus WL, Kliewer SA, Mangelsdorf DJ
Proc Natl Acad Sci U S A 2025 Jun;122(22):e2505263122