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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
要旨

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.

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Sigma-Aldrich
モノクローナル抗FLAG® M1 マウス宿主抗体, clone M1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
SB 203580, solid, ≥98% (HPLC)
Sigma-Aldrich
アデノシン 3′,5′-環状一リン酸 トリス塩, ≥97% (HPLC), powder