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

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


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."

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Endocrine System / drug effects
  • Endocrine System / metabolism*
  • Feeding Behavior / drug effects
  • Fibroblast Growth Factors / metabolism*
  • Food Preferences / drug effects*
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Mice, Knockout
  • Nuclear Proteins / metabolism
  • Signal Transduction / drug effects
  • Sucrose / pharmacology*
  • Taste / drug effects*
  • Transcription Factors / metabolism


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Mlxipl protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • fibroblast growth factor 21
  • Sucrose
  • Fibroblast Growth Factors