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Cell Metab. 2018 Jun 5;27(6):1338-1347.e4. doi: 10.1016/j.cmet.2018.04.001. Epub 2018 Apr 12.

The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and Alcohol.

Author information

1
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
2
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, TX 75390, USA.
3
Departments of Biochemistry and Molecular Biophysics and Neuroscience, Columbia College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
4
Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX 75390, USA.
5
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.
6
Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria.
7
Department of Transplantation Surgery, Medical University of Graz, 8036 Graz, Austria; Center for Biomarker Research in Medicine (CBmed), 8010 Graz, Austria.
8
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, TX 75390, USA.
9
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
10
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: davo.mango@utsouthwestern.edu.
11
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: steven.kliewer@utsouthwestern.edu.

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.

KEYWORDS:

FGF21; alcohol; hypothalamus; ketogenic diet; neurons; water drinking; β-adrenergic signaling; β-klotho

Comment in

PMID:
29657029
PMCID:
PMC5990458
DOI:
10.1016/j.cmet.2018.04.001
[Indexed for MEDLINE]
Free PMC Article

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