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  • Internalization-Dependent Free Fatty Acid Receptor 2 Signaling Is Essential for Propionate-Induced Anorectic Gut Hormone Release.

Internalization-Dependent Free Fatty Acid Receptor 2 Signaling Is Essential for Propionate-Induced Anorectic Gut Hormone Release.

iScience (2020-08-28)
Natarin Caengprasath, Noemi Gonzalez-Abuin, Maria Shchepinova, Yue Ma, Asuka Inoue, Edward W Tate, Gary Frost, Aylin C Hanyaloglu
ABSTRACT

The ability of propionate, a short-chain fatty acid produced from the fermentation of non-digestible carbohydrates in the colon, to stimulate the release of anorectic gut hormones, such as glucagon like peptide-1 (GLP-1), is an attractive approach to enhance appetite regulation, weight management, and glycemic control. Propionate induces GLP-1 release via its G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFA2), a GPCR that activates Gαi and Gαq/11. However, how pleiotropic GPCR signaling mechanisms in the gut regulates appetite is poorly understood. Here, we identify propionate-mediated G protein signaling is spatially directed within the cell whereby FFA2 is targeted to very early endosomes. Furthermore, propionate activates a Gαi/p38 signaling pathway, which requires receptor internalization and is essential for propionate-induced GLP-1 release in enteroendocrine cells and colonic crypts. Our study reveals that intestinal metabolites engage membrane trafficking pathways and that receptor internalization could orchestrate complex GPCR pathways within the gut.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Adenosine 3′,5′-cyclic monophosphate tris salt, ≥97% (HPLC), powder
Sigma-Aldrich
Monoclonal ANTI-FLAG® M1 antibody produced in mouse, clone M1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
SB 203580, solid, ≥98% (HPLC)