@article{d981a639d6ae46c6acf7c9c298b64879,
title = "The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and Alcohol",
abstract = "Alcohol and ketogenic diets increase water consumption. Here, we show that the hormone FGF21 is required for this drinking response in mice. Circulating levels of FGF21 are increased by alcohol consumption in humans and by both alcohol and ketogenic diets in mice. Pharmacologic administration of FGF21 stimulates water drinking behavior in mice within 2 hr. Concordantly, mice lacking FGF21 fail to increase water intake in response to either alcohol or a ketogenic diet. The effect of FGF21 on drinking is mediated in part by SIM1-positive neurons of the hypothalamus and is inhibited by β-adrenergic receptor antagonists. Given that FGF21 also is known to suppress alcohol intake in favor of pure water, this work identifies FGF21 as a fundamental neurotropic hormone that governs water balance in response to specific nutrient stresses that can cause dehydration. Song et al. show that the metabolic hormone FGF21 is involved in water drinking in response to metabolic stresses, such as alcohol intake and ketogenic diets, which can cause dehydration. The effect of FGF21 on water balance is mediated by a hypothalamic circuit that is dependent on β-adrenergic signaling.",
keywords = "FGF21, alcohol, hypothalamus, ketogenic diet, neurons, water drinking, β-adrenergic signaling, β-klotho",
author = "Parkyong Song and Zechner, {Christoph Peter Gerhard} and Genaro Hernandez and Jos{\'e} C{\'a}novas and Yang Xie and Varun Sondhi and Martin Wagner and Vanessa Stadlbauer and Angela Horvath and Bettina Leber and Hu, {Ming C} and Moe, {Orson W} and Mangelsdorf, {David J} and Kliewer, {Steven A}",
note = "Funding Information: We thank Charles Zuker for discussions, Birgitte Anderson and Novo Nordisk for providing recombinant FGF21, Richard Auchus (University of Michigan) for advice about the aldosterone assay, Yuan Zhang for technical assistance, and Rui Chen and Farah Ammouri for their help with the brain histology and quantification. This work was supported by the Center for Biomarker Research in Medicine, a COMET K1 center funded by the Austrian Research Promotion Agency, FFG (M.W., V. Stadlbauer, A.H., and B.L.); a PEW Latin American Fellowship (J.C.); the National Institutes of Health (K08DK106569 to C.Z.; P30DK079328 to O.W.M.; 1R01GM115473 to Y.X.; R01DK091392, R01DK092461, and R01HL134373 to M.C.H. and O.W.M.; R01DK067158 and P01AG051459 to S.A.K. and D.J.M.); the Robert A. Welch Foundation (grants I-1558 to S.A.K. and I-1275 to D.J.M.); the Cancer Prevention and Research Institute of Texas (RP120732 to Y.X.); the National Science Foundation Graduate Research Fellowship Program (G.H.); the Pak Foundation (M.C.H. and O.W.M.); and the Howard Hughes Medical Institute (D.J.M.). Funding Information: We thank Charles Zuker for discussions, Birgitte Anderson and Novo Nordisk for providing recombinant FGF21, Richard Auchus (University of Michigan) for advice about the aldosterone assay, Yuan Zhang for technical assistance, and Rui Chen and Farah Ammouri for their help with the brain histology and quantification. This work was supported by the Center for Biomarker Research in Medicine , a COMET K1 center funded by the Austrian Research Promotion Agency , FFG (M.W., V. Stadlbauer, A.H., and B.L.); a PEW Latin American Fellowship (J.C.); the National Institutes of Health ( K08DK106569 to C.Z.; P30DK079328 to O.W.M.; 1R01GM115473 to Y.X.; R01DK091392 , R01DK092461 , and R01HL134373 to M.C.H. and O.W.M.; R01DK067158 and P01AG051459 to S.A.K. and D.J.M.); the Robert A. Welch Foundation (grants I-1558 to S.A.K. and I-1275 to D.J.M.); the Cancer Prevention and Research Institute of Texas ( RP120732 to Y.X.); the National Science Foundation Graduate Research Fellowship Program (G.H.); the Pak Foundation (M.C.H. and O.W.M.); and the Howard Hughes Medical Institute (D.J.M.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = jun,
day = "5",
doi = "10.1016/j.cmet.2018.04.001",
language = "English (US)",
volume = "27",
pages = "1338--1347.e4",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "6",
}