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

163 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
Journal	Cell Metabolism
Volume	23
Issue number	2
Pages (from-to)	335-43
Number of pages	9
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2015.12.003
Publication status	Published - 9 Feb 2016

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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), 335-43. https://doi.org/10.1016/j.cmet.2015.12.003

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. 335-43. https://doi.org/10.1016/j.cmet.2015.12.003

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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}",

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

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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 - Journal 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

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