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

Stephanie von Holstein-Rathlou; Lucas D BonDurant; Lila Peltekian; Meghan C Naber; Terry C Yin; Kristin E Claflin; Adriana Ibarra Urizar; Andreas N Madsen; Cecilia Ratner; Birgitte Holst; Kristian Karstoft; Aurelie Vandenbeuch; Catherine B Anderson; Martin D Cassell; Anthony P Thompson; Thomas P Solomon; Kamal Rahmouni; Sue C Kinnamon; Andrew A Pieper; Matthew P Gillum; Matthew J Potthoff

doi:10.1016/j.cmet.2015.12.003

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

Journal article

Open access

Peer reviewed

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

Stephanie von Holstein-Rathlou, Lucas D BonDurant, Lila Peltekian, Meghan C Naber, Terry C Yin, Kristin E Claflin, Adriana Ibarra Urizar, Andreas N Madsen, Cecilia Ratner, Birgitte Holst, …

Cell metabolism, Vol.23(2), pp.335-343

02/09/2016

DOI: 10.1016/j.cmet.2015.12.003

PMCID: PMC4756759

PMID: 26724858

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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."

Food Preferences - drug effects

Liver - metabolism

Sucrose - pharmacology

Male

Nuclear Proteins - metabolism

Feeding Behavior - drug effects

Mice, Knockout

Transcription Factors - metabolism

Fibroblast Growth Factors - metabolism

Animals

Taste - drug effects

Liver - drug effects

Signal Transduction - drug effects

Endocrine System - metabolism

Endocrine System - drug effects

Details

Title: Subtitle: FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver
Creators: Stephanie von Holstein-Rathlou - Section for Metabolic Imaging and Liver Metabolism, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Lucas D BonDurant - 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
Lila Peltekian - 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
Meghan C Naber - 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
Terry C Yin - 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
Kristin E Claflin - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Adriana Ibarra Urizar - Section for Metabolic Imaging and Liver Metabolism, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Andreas N Madsen - 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
Cecilia Ratner - 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
Birgitte Holst - 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
Kristian Karstoft - Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark
Aurelie Vandenbeuch - Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Catherine B Anderson - Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Martin D Cassell - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Anthony P Thompson - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Thomas P Solomon - 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
Kamal Rahmouni - 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
Sue C Kinnamon - Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Andrew A Pieper - 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
Matthew P Gillum - 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
Matthew J Potthoff - 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
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.23(2), pp.335-343
Publisher: United States
DOI: 10.1016/j.cmet.2015.12.003
PMID: 26724858
PMCID: PMC4756759
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: R01 DK106104 / NIDDK NIH HHS T32 GM067795 / NIGMS NIH HHS R01DK106104 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS P30 DC004657 / NIDCD NIH HHS
Language: English
Date published: 02/09/2016
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Anatomy and Cell Biology; Iowa Neuroscience Institute; Radiation Oncology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040357002771

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