The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents

TLDR

Peptide YY and GLP‑1 are gut hormones that acutely suppress appetite, and the SCFA receptor FFA2 expressed on colonic L cells has been implicated in appetite regulation. The study aimed to characterize the in vitro and in vivo effects of colonic propionate on PYY and GLP‑1 release in rodents and to determine whether FFA2 mediates these effects using FFA2 knockout mice. Researchers used isolated colonic crypt cultures and a novel in vivo portal‑vein sampling technique following colonic propionate infusion to assess hormone release in wild‑type and FFA2‑deficient mice. Propionate stimulated PYY and GLP‑1 secretion in wild‑type cultures and in vivo, but this response was significantly reduced or absent in FFA2‑knockout mice, demonstrating that FFA2 is essential for SCFA‑induced gut hormone release.

Abstract

The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro and in vivo effects of colonic propionate on PYY and GLP-1 release in rodents, and investigate the role of FFA2 in mediating these effects using FFA2 knockout mice.We used Wistar rats, C57BL6 mice and free fatty acid receptor 2 knockout (FFA(-/-)) mice on a C57BL6 background to explore the impact of the SCFA propionate on PYY and GLP-1 release. Isolated colonic crypt cultures were used to assess the effects of propionate on gut hormone release in vitro. We subsequently developed an in vivo technique to assess gut hormone release into the portal vein following colonic infusion of propionate.Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2(-/-) mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2(-/-) mice.Intra-colonic administration of propionate stimulates the concurrent release of both GLP-1 and PYY in rats and mice. These data demonstrate that FFA2 deficiency impairs SCFA-induced gut hormone secretion both in vitro and in vivo.