Presence of luminal acetate sensing and absorption mechanisms in rat duodenum

Abstract

Duodenal lumen short‐chain fatty acids (SCFA) are derived from ingested food or bacteria. Since SCFA receptors GPR41 and 43 are expressed on duodenal endocrine cells, and since a selective GPR43 agonist increases duodenal HCO3− secretion (DBS) via muscarinic/5‐HT4 receptor activation, we further examined the effect of luminal acetate on DBS. We measured DBS with pH and CO2 electrodes in a perfused duodenal loop in anesthetized rats. GPR41 colocalized with glucagon‐like peptide (GLP)‐1, whereas GPR43 colocalized with 5‐HT. Luminal perfusion of acetate dose‐dependently increased DBS with increasing GLP‐2 release. Acetate‐induced DBS was reduced by the 5‐HT4 receptor antagonist GR113808, pretreatment with indomethacin or high‐dose capsaicin, or co‐perfusion of the monocarboxylate transporter (MCT) inhibitor 4‐CHCA. Na+‐coupled MCT‐1 (SMCT1) was localized on the brush border and MCT4 on the basolateral membrane of upper villous epithelial cells, whereas MCT1 was expressed on the basolateral membrane of lower villous and crypt cells. Feeding increased the membrane localization of MCT1 and 4 with increased mRNA expression, compared to overnight fasting. Luminal acetate‐induced DBS via GLP‐2, 5‐HT, prostaglandin and capsaicin pathways, and acetate absorption via SMCT1 and MCT, may be implicated in the pathogenesis of functional dyspepsia and bacterial overgrowth. VA Merit Review, NIH‐NIDDK R01 DK54221