Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

Am J Physiol Gastrointest Liver Physiol. 2019 May 1;316(5):G574-G584. doi: 10.1152/ajpgi.00010.2019. Epub 2019 Feb 15.

Abstract

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion. NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.

Keywords: TGR5; bile acids; colon; glucagon-like-peptide 1; peptide-YY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Carrier Proteins / metabolism*
  • Colon / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Ileum / metabolism
  • Intestinal Absorption / physiology
  • L Cells
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Peptide YY / metabolism*
  • Rats

Substances

  • Bile Acids and Salts
  • Carrier Proteins
  • Membrane Glycoproteins
  • bile acid binding proteins
  • Peptide YY
  • Glucagon-Like Peptide 1