Free fatty acids induce cholecystokinin secretion through GPR120

Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):523-7. doi: 10.1007/s00210-007-0200-8. Epub 2007 Oct 31.


The ingestion of fat induces secretion of the gut peptide hormone cholecystokinin (CCK); however, the mechanism responsible for lipid-induced CCK release remains unknown. Recently, a group of free fatty acid (FFA) receptors, which includes the long-chain FFA receptors GPR120 and GPR40, has been identified. In this study, we examined whether these FFA receptors mediate lipid-induced CCK release in the mouse. We first observed that intra-gastric administration of long-chain FFAs increased plasma CCK levels. Using mouse enteroendocrine STC-1 cells as a model system, we further studied the mechanism of this FFA-induced CCK secretion. Long-chain FFAs promoted CCK secretion from STC-1 cells, which was abolished either by removal of extracellular Ca2+ or by the L-type Ca2+ channel blocker nicardipine. Furthermore, this FFA-induced CCK secretion was specifically inhibited by transfection of GPR120-specific, but not GPR40-specific, short hairpin RNA. These results indicate that long-chain FFAs induce CCK secretion through GPR120-coupled Ca2+ signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Cell Line
  • Cholecystokinin / drug effects*
  • Cholecystokinin / metabolism
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism
  • Fatty Acids, Nonesterified / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / metabolism
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, G-Protein-Coupled / physiology*
  • Transfection


  • FFAR4 protein, mouse
  • Fatty Acids, Nonesterified
  • Ffar1 protein, mouse
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Cholecystokinin