Short-chain fatty acids: possible regulators of insulin secretion

Mol Cell Biochem. 2023 Mar;478(3):517-530. doi: 10.1007/s11010-022-04528-8. Epub 2022 Aug 9.

Abstract

The benefits of gut microbiota-derived short-chain fatty acids (SCFAs) towards health and metabolism have been emerging since the past decade. Extensive studies have been carried out to understand the mechanisms responsible in initiating the functionalities of these SCFAs towards body tissues, which greatly involves the SCFA-specific receptors free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). This review intends to discuss the potential of SCFAs particularly in regulating insulin secretion in pancreatic β-cells, by explaining the production of SCFAs in the gut, the fate of each SCFAs after their production, involvement of FFAR2 and FFAR3 signalling mechanisms and their impacts on insulin secretion. Increased secretion of insulin after SCFAs treatments were reported in many studies, but contradicting evidence also exist in several other studies. Hence, no clear consensus was achieved in determining the true potential of SCFA in regulating insulin secretion. In this review, we explore how such differences were possible and hopefully be able to shed some perspectives in understanding SCFAs-signalling behaviour and preferences.

Keywords: FFAR2; FFAR3; G-protein coupled receptor (GPCR); Glucose-stimulated insulin secretion (GSIS); Gαq/11-signalling mechanism; Short-chain fatty acids (SCFAs).

Publication types

  • Review

MeSH terms

  • Fatty Acids, Nonesterified*
  • Fatty Acids, Volatile / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Receptors, G-Protein-Coupled* / metabolism

Substances

  • Receptors, G-Protein-Coupled
  • Fatty Acids, Nonesterified
  • Fatty Acids, Volatile
  • Insulin