MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m6A-YTHDF1-dependent mechanism

Abstract

Intramuscular fat is consideredapotential factor that is associated withmeat qualityinanimalproduction and insulin resistance in humans. N6-methyladenosine (m6A) modification of mRNA plays an important role in regulating adipogenesis. However, the effects of m6A on the adipogenesis of intramuscular preadipocytes and associated mechanisms remain unknown.Here,we performedm6Asequencing to comparem6Amethylome of the longissimus dorsi muscles (LDMs) between Landrace pigs (lean-type breed) and Jinhua pigs (obese-type breedwith higher levels of intramuscular fat). Transcriptome-widem6Aprofiling of porcine LDMswas highly conservedwith humans andmice.Furthermore,we identifiedauniquemethylated gene inJinhua pigsnamedmitochondrial carrier homology 2 (MTCH2). Them6Alevels ofMTCH2mRNAwere reduced by introducing a synonymousmutation, and adipogenesis test results showed that the MTCH2 mutant was inferior with regard to adipogenesis compared with the MTCH2 wild-type.We then found that MTCH2 protein expression was positively associated with m6A levels, and an YTHdomain family protein 1-RNA immunoprecipitation-quantitative PCR assay indicated that MTCH2 mRNAwas a target of the YTH domain family protein 1. This study provides comprehensivem6Aprofiles of LDM transcriptomes in pigs and suggests an essential role for m6A modification of MTCH2 in intramuscular fat regulation.