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

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 GillumMatthew J Potthoff

Research output: Contribution to journal › Article › peer-review

164 Citations (Scopus)

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."

Original language	English
Pages (from-to)	335-343
Journal	Cell Metabolism
Volume	23
Issue number	2
Early online date	24 Dec 2015
DOIs	https://doi.org/10.1016/j.cmet.2015.12.003
Publication status	Published - 9 Feb 2016

Access to Document

10.1016/j.cmet.2015.12.003Licence: None: All rights reserved

Cite this

von Holstein-Rathlou, S., BonDurant, L. D., Peltekian, L., Naber, M. C., Yin, T. C., Claflin, K. E., Urizar, A. I., Madsen, A. N., Ratner, C., Holst, B., Karstoft, K., Vandenbeuch, A., Anderson, C. B., Cassell, M. D., Thompson, A. P., Solomon, T. P., Rahmouni, K., Kinnamon, S. C., Pieper, A. A., ... Potthoff, M. J. (2016). FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver. Cell Metabolism, 23(2), 335-343. Advance online publication. https://doi.org/10.1016/j.cmet.2015.12.003

@article{b08e8e6e531c4bc7ba91b1cffc4cb6db,

title = "FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver",

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.{"}",

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

year = "2016",

month = feb,

day = "9",

doi = "10.1016/j.cmet.2015.12.003",

language = "English",

volume = "23",

pages = "335--343",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Elsevier",

number = "2",

}

von Holstein-Rathlou, S, BonDurant, LD, Peltekian, L, Naber, MC, Yin, TC, Claflin, KE, Urizar, AI, Madsen, AN, Ratner, C, Holst, B, Karstoft, K, Vandenbeuch, A, Anderson, CB, Cassell, MD, Thompson, AP, Solomon, TP, Rahmouni, K, Kinnamon, SC, Pieper, AA, Gillum, MP & Potthoff, MJ 2016, 'FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver', Cell Metabolism, vol. 23, no. 2, pp. 335-343. https://doi.org/10.1016/j.cmet.2015.12.003

TY - JOUR

T1 - FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver

AU - von Holstein-Rathlou, Stephanie

AU - BonDurant, Lucas D

AU - Peltekian, Lila

AU - Naber, Meghan C

AU - Yin, Terry C

AU - Claflin, Kristin E

AU - Urizar, Adriana Ibarra

AU - Madsen, Andreas N

AU - Ratner, Cecilia

AU - Holst, Birgitte

AU - Karstoft, Kristian

AU - Vandenbeuch, Aurelie

AU - Anderson, Catherine B

AU - Cassell, Martin D

AU - Thompson, Anthony P

AU - Solomon, Thomas P

AU - Rahmouni, Kamal

AU - Kinnamon, Sue C

AU - Pieper, Andrew A

AU - Gillum, Matthew P

AU - Potthoff, Matthew J

PY - 2016/2/9

Y1 - 2016/2/9

N2 - 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."

AB - 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."

U2 - 10.1016/j.cmet.2015.12.003

DO - 10.1016/j.cmet.2015.12.003

M3 - Article

C2 - 26724858

SN - 1550-4131

VL - 23

SP - 335

EP - 343

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

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

Abstract

Access to Document

Fingerprint

Cite this