Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion

Endocrinology. 2015 Mar;156(3):837-46. doi: 10.1210/en.2014-1653. Epub 2014 Dec 23.


Gastric inhibitory polypeptide (GIP) is an incretin secreted from enteroendocrine K cells in response to meal ingestion. Recently free fatty acid receptor G protein-coupled receptor (GPR) 120 was identified as a lipid sensor involved in glucagon-like peptide-1 secretion. However, Gpr 120 gene expression and its role in K cells remain unclear, partly due to difficulties in separation of K cells from other intestinal epithelial cells. In this study, we purified K cells using GIP-green fluorescent protein (GFP) knock-in mice, in which K cells can be visualized by GFP fluorescence. GFP-positive cells (K cells) were observed in the small intestine but not in the stomach and colon. K cell number and GIP content in K cells were significantly higher in the upper small intestine than those in the lower small intestine. We also examined the expression levels of several free fatty acid receptors in K cells. Among free fatty acid receptors, GPR120 was highly expressed in the K cells of the upper small intestine compared with the lower small intestine. To clarify the role of GPR120 on K cells in vivo, we used GPR120-deficient mice (GPR120(-/-)). GPR120(-/-) exhibited significantly lower GIP secretion (75% reduction, P < .01) after lard oil ingestion compared with that in wild-type mice. Consistently, pharmacological inhibition of GPR120 with grifolic acid methyl ether in wild-type mice significantly attenuated lard oil-induced GIP secretion. In conclusion, GPR120 is expressed abundantly in K cells of the upper small intestine and plays a critical role in lipid-induced GIP secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Fats
  • Enteroendocrine Cells / metabolism*
  • Gastric Inhibitory Polypeptide / metabolism*
  • Gene Expression Regulation / physiology
  • Glucose Tolerance Test
  • Green Fluorescent Proteins
  • Intestinal Mucosa
  • Intestine, Small / cytology*
  • Intestine, Small / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salicylates / pharmacology
  • Sesterterpenes / pharmacology


  • Dietary Fats
  • FFAR4 protein, mouse
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Salicylates
  • Sesterterpenes
  • grifolic acid methyl ether
  • Green Fluorescent Proteins
  • Gastric Inhibitory Polypeptide
  • lard