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Cell Metab. 2016 Feb 9;23(2):335-43. doi: 10.1016/j.cmet.2015.12.003. Epub 2015 Dec 24.

FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver.

Author information

1
Section for Metabolic Imaging and Liver Metabolism, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
2
Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
3
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
4
Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
5
Section for Metabolic Receptology and Enteroendocrinology, the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
6
Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark.
7
Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
8
Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
9
Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; School of Sport, Exercise, and Rehabilitation Sciences, and Institute of Metabolism and Systems Research, University of Birmingham, UK.
10
Section for Metabolic Imaging and Liver Metabolism, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: gillum@sund.ku.dk.
11
Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: matthew-potthoff@uiowa.edu.

Abstract

The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude that the liver functions to regulate macronutrient-specific intake by producing an endocrine satiety signal that acts centrally to suppress the intake of "sweets."

PMID:
26724858
PMCID:
PMC4756759
DOI:
10.1016/j.cmet.2015.12.003
[Indexed for MEDLINE]
Free PMC Article

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