A novel anti-inflammatory role of GPR120 in intestinal epithelial cells

Am J Physiol Cell Physiol. 2016 Apr 1;310(7):C612-21. doi: 10.1152/ajpcell.00123.2015. Epub 2016 Jan 20.

Abstract

GPR120 (free fatty acid receptor-4) is a G protein-coupled receptor for medium- and long-chain unsaturated fatty acids, including ω-3 fatty acids. Recent studies have shown GPR120 to play cardinal roles in metabolic disorders via modulation of gut hormone secretion and insulin sensitivity and to exert anti-inflammatory effects in macrophages and adipose tissues. However, information on anti-inflammatory role of GPR120 at the level of intestinal epithelium is very limited. Current studies demonstrated differential levels of GPR120 mRNA and protein along the length of the human, mouse, and rat intestine and delineated distinct anti-inflammatory responses following GPR120 activation in model human intestinal epithelial Caco-2 cells, but not in model mouse intestinal epithelial endocrine cell line STC-1. In Caco-2 cells, GPR120 was internalized, bound to β-arrestin-2, and attenuated NF-κB activation in response to 30-min exposure to the agonists GW9508, TUG-891, or docosahexaenoic acid. These effects were abrogated in response to small interfering RNA silencing of β-arrestin-2. Treatment of STC-1 cells with these agonists did not induce receptor internalization and had no effects on NF-κB activation, although treatment with the agonists GW9508 or TUG-891 for 6 h augmented the synthesis and secretion of the gut hormone glucagon-like peptide-1 in this cell line. Our studies for the first time demonstrated a GPR120-mediated novel anti-inflammatory pathway in specific intestinal epithelial cell types that could be of therapeutic relevance to intestinal inflammatory disorders.

Keywords: Caco-2; FFAR4; GLP-1; NF-κB; STC-1.

Publication types

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

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Inflammation / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, G-Protein-Coupled / immunology*
  • Receptors, G-Protein-Coupled / metabolism
  • Transfection

Substances

  • FFAR4 protein, human
  • FFAR4 protein, mouse
  • Ffar4 protein, rat
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled