Exosomal miR‐122 promotes adipogenesis and aggravates obesity through the VDR/SREBF1 axis

Abstract Objective This study examined the effects of miR‐122–enriched exosomes on the expression of vitamin D3 receptor (VDR) and sterol regulatory element‐binding transcription factor 1 (SREBF1) and their roles during adipogenesis. Methods The roles of miR‐122, SREBF1, and VDR were investigated during adipogenesis. The relationships between VDR and miR‐122 or SREBF1 were assessed by dual‐luciferase reporter and chromatin immunoprecipitation assays. The potential role of miR‐122/VDR/SREBF1 was evaluated in high‐fat diet‐induced obese male mice. Results High levels of miR‐122 were found only in adipose tissue‐derived exosomes (Exo‐AT) and Exo‐AT–treated cells. Overexpression of miR‐122 promoted adipogenesis, and inhibition of miR‐122 prevented adipogenesis by regulating VDR, SREBF1, peroxisome proliferator‐activated receptor gamma, lipoprotein lipase, and adiponectin. Knockdown of Srebf1 or overexpression of VDR could inhibit adipogenesis. However, exosomal miR‐122 could reverse their inhibitory effects. The dual‐luciferase reporter assay and chromatin immunoprecipitation assays confirmed that VDR was a direct target of miR‐122. It could bind to the BS1 region of the SREBF1 promoter and inhibit SREBF1 expression. Moreover, miR‐122 inhibition could alleviate obesity in high‐fat diet‐induced obese male mice, possibly through upregulating the VDR/SREBF1 axis. Conclusion MiR‐122–enriched Exo‐AT promoted adipogenesis by regulating the VDR/SREBF1 axis.