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 journalArticlepeer-review

164 Citations (Scopus)


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 languageEnglish
Pages (from-to)335-343
JournalCell Metabolism
Issue number2
Early online date24 Dec 2015
Publication statusPublished - 9 Feb 2016


Dive into the research topics of 'FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver'. Together they form a unique fingerprint.

Cite this