Short-Chain Fatty Acid Release of Peptide YY in the Isolated Rabbit Distal Colon

Abstract

Short-chain fatty acids (SCFAs) form the major ionic fraction of stool, provide the major metabolic substrate for colonic epithelium, and promote mucosal ion transport. Despite this prominent role of SCFAs in metabolism of the colon, their effect on colonic endocrine cell function has not been studied. Consequently, we hypothesized that SCFAs might modulate release of peptide YY (PYY) from colonic type-L endocrine cells. The specific aims of this study were to measure release of PYY from the isolated perfused rabbit distal colon stimulated by intraluminal infusion of 0.9% saline, acetate (10 mM), acetoacetate (10 mM), n-butyrate (1, 3.3, 10, 100 mM), and pyruvate (10 mM). PYY levels were measured by radioimmunoassay in the venous effluent of the rabbit colon. All four SCFAs (10 mM) caused at least a twofold increase in integrated release of PYY from the isolated perfused rabbit colon. Graded concentrations of n-butyrate caused a stepwise release of PYY. This study suggests that SCFAs may modulate the release of colonic PYY in rabbits.

Peptide YY, Glucagon-Like Peptide-1, and Neurotensin Responses to Luminal Factors in the Isolated Vascularly Perfused Rat Ileum

“…Our results agree with a previous in vivo study that reported that a mixture of SCFAs injected into the rat ileum released insignificant amounts of PYY, whereas it was potent in the colon (12). For comparison, SCFAs caused a release of PYY from the isolated vascularly colon of rats and rabbits (26,31). Interestingly, none of these SCFAs produced any release of GLP-1 in the rat colonic preparation (25).…”

Roles of Short-Chain Fatty Acids and their Receptors in Colonic Motility

“…Therefore, the majority of PYY-containing enteroendocrine cells probably express FFA2 as SCFAs sensors, and SCFAs might stimulate PYY release through FFA2. This is supported by the observation that acetate, which is selective for FFA2, has been reported to cause an increase in the release of PYY (34). Since SCFAs are produced by bacterial fermentation of the carbohydrates of dietary fiber in the large intestinal lumen as mentioned above, the presence of SCFAs or individual ratios of SCFAs in the colonic lumen may reflect the activity of luminal bacterial flora and SCFA receptors and possibly monitor the activity of bacteria to maintain colonic health.…”

“…These results suggest that FFA2 may be involved in the regulation of lipid homeostasis through the inhibition of lipolysis. For the signal transduction, FFA2 and FFA3 are coupled to the formation of inositol 1,4,5-triphosphate, intracellular Ca 2+ mobilization, the activation of ERK 1/2, and the inhibition of intracellular cAMP accumulation (34). However, FFA2 and FFA3 exhibit differential coupling to G-proteins; FFA3 couples exclusively through the pertussis toxin-sensitive G i/o family, whereas FFA2 couples through the G i/o and pertussis toxin-insensitive G q family (5).…”

Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms?

“…The discovery that FFAR2 and FFAR3 are co-localised with L-cells in the colon has led to the suggestion that activation of these receptors by SCFA ligands would facilitate PYY and GLP-1 release. Investigations using rodent primary colonic cultures have consistently shown that SCFA stimulate the release of PYY and GLP-1 from colonic L-cells (50)(51)(52)(53) . Tolhurst et al (53) observed that SCFA activation stimulated GLP-1 secretion from wild-type murine L-cells and these effects were significantly attenuated in FFAR2 knock-out (−/−) and FFAR3 −/− cells.…”