Exosomal miR‐122 promotes adipogenesis and aggravates obesity through the VDR/SREBF1 axis
Xiao‐Yan Huang, Ji‐Xiong Chen, Yi Ren, Li‐Chun Fan, Wei Xiang, Xiaojie He
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.