Differential expression of miRNAs during white adipose tissue browning induced by different methods and its potential regulatory mechanisms / 中华老年医学杂志

ABSTRACT

Objective:To investigate the differential expression of miRNAs during white adipose tissue(WAT)browning in mice under different stimulation conditions, and to analyze the potential regulatory mechanisms.Methods:Mouse models of subcutaneous WAT(sWAT)browning were established by different methods: cold-induced browning and intraperitoneal injection of CL316-243.HE staining and analysis of thermogenesis-related gene expression were used to validate the browning models.miRNAs expression profiles in different conditions were described by RNA-sequencing(RNA-seq)and miRNAs with similar expression patterns in the two groups were detected via screening.Target genes of miRNAs were predicted by bioinformatics, and their expression levels were verified by quantitative real-time PCR(qRT-PCR).Results:Both cold-induced browning and intraperitoneal injection of CL316-243 were able to activate the browning of sWAT, and the miRNA expression profile of sWAT showed significant differences before and after induction.After screening differentially expressed miRNAs, the expression of Mir-30E-3p was increased and the expression of Mir-181A-5p was decreased under different browning-inducing conditions in WAT.The prediction and validation of target genes revealed that cyclin-dependent kinase 6(Cdk6)and sirtuin 1(Sirt1)were potential targets regulated by miR-30e-3p and miR-181a-5p in the browning of sWAT, respectively.Conclusions:There are significant differences in miRNA expression during the browning of sWAT in mice induced by cold stimulation and CL316-243 injection.MiR-30e-3p and miR-181a-5p may be involved in the regulation of the sWAT browning process through target genes Cdk6 and Sirt1, respectively.