Roles of miR-124-3p/Scd1 in urolithin A-induced brown adipocyte differentiation and succinate-dependent regulation of mitochondrial complex II

Abstract

Brown adipocytes have been linked to managing human obesity and related metabolic diseases. A large number of natural products have emerged that can activate brown adipocytes tissue (BAT) to active thermogenesis, but the epigenetic mechanisms have not been fully resolved. In this study, we identified the induction of miR-124-3p by urolithin A (UA) as a means to increase the thermogenic activity of brown adipocytes. Overexpression of miR-124-3p enhances thermogenesis by increasing mitochondrial content in brown adipocytes. Mechanistically, to clarify that miR-124-3p affects fatty acid synthesis using bioinformatics methods, it is clear that miR-124 affects the synthesis of fatty acids through the enrichment analysis of the KEGG pathway, and using dual luci. ferase to determine the target gene as stearoyl-CoA desaturase 1 (SCD1) while controlling rates of fatty acids synthesis and de novo brown fat biogenesis. Finally, in the overexpression of miR-124-3p and UA-treated BAT, succinate accumulation was enhanced in cells and fueled mitochondrial complex II activities. This study highlights a miR-124-3p/SCD1/succinate pathway that stimulates thermogenesis of BAT via the modulatory roles of UA.

Keywords: Mitochondrial complex II; SCD1; Succinate; Urolithin A; miR-124-3p.