5 years ago

The short-chain fatty acid propionate inhibits adipogenic differentiation of human chorion-derived mesenchymal stem cells through the free fatty acid receptor 2.

Bay, Horváth, Kovács, Dombrádi, Sipos, Lontay, Tamás, Major, Iván
Free fatty acid receptor 2 (FFAR2, also known as GPR43) is a G-protein-coupled receptor activated by short-chain fatty acids that are produced by gut microbiota through fermentation of non-digestible carbohydrates. FFAR2 functions as a metabolic sensor and is expressed in metabolically active tissues, such as adipose tissue. Earlier studies proved the connection between FFAR2 and adipocyte differentiation in mice. The aim of this study was to investigate the implication of FFAR2 receptor in adipogenesis in human chorion-derived mesenchymal stem cells (cMSCs). The short-chain fatty acid, propionate, and a selective synthetic phenylacetamide FFAR2 agonist resulted in a marked suppression of lipid droplet accumulation during the adipogenic differentiation of cMSCs. Protein expression studies revealed that FFAR2 was detectable at any time point of the differentiation period. The direct involvement of FFAR2 in the differentiation into adipocytes was proven by the downregulation of its gene expression in cMSCs by lentiviral transduction particles. Our results showed a significant suppression in lipid accumulation upon propionate and FFAR2 agonist treatments was elicited by FFAR2-silencing. Based on these results we suggest that propionate inhibits the formation of adipocytes from MSCs and acts on adipogenesis predominantly via FFAR2.

Publisher URL: http://doi.org/10.1089/scd.2017.0035

DOI: 10.1089/scd.2017.0035

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