GPR91 Mediates Succinate Regulation Of Skeletal Muscle Oxidative Metabolism And Muscle Fiber Type Switch

The type of muscle fibers is closely related to the body's energy metabolism and the formation of meat quality.The different composition of muscle fiber type is influenced by many factors,such as heredity,hormones,nutrition,exercise and so on.Among these,exercise is a key factor,which could alter metabolitesin tricarboxylic acid cyclic(TAC),especially succinate(SUA)improved significantly.Therefore,the aim of this study is to explore the effect of SUA on the metabolism and switch of skeletal muscle fibers and to reveal its potential mechanism.In order to study the effect of SUA onthe metabolism and switchingof skeletal muscle fibers in vivo and in vitro.In vivo,we selected 33 C57 BL / 6J mice to divided into three groups randomly.Then analyzed the body composition,treadmill,claw gripping of mice exercise.The total enzyme activityof succinate dehydrogenase,hexokinase a nd lactate dehydrogenase were measured in gastrocnemius.Western blot and quantitative PCR were used to detect the expression of muscle fiber type and metabolism related proteinsandgenes in the gastrocnemius muscle of mice.In vitro,we cultured C2C12 cell until 80%-90% in 10% FCS,and replaced mediumwith 2% horse serum to induce differentiation for 6 days.At last,SUA treated C2C12 cell for 48 h.The results indicated that:(1)After 8 weeks of succinate supplementation,the running time and claw grip were significantly increased in mice,and activated the Calcineurin pathway,leading to increase the Calcineurin and MEF2 a,NFAT protein expression and translocation.At the same time,the PGC-1?,NRF1 and other protein expression were improved to promote the formation of mitochondria,and skeletal muscle oxidative metabolism.(2)2 mM succinate treated C2C12 cells for 48 h,could significantly increase Calcineurin,MEF2 a,NFAT,PGC-1?,NRF1 protein expression,enzyme activity related to oxidative metabolism,thereby increasing the slow muscle fibers and mitocho ndria.To further to detected the mechanism of SUA on the effect of skeletal muscle fiber type transformation.This study used the interference of SUA receptor(GPR91)in cells and mice,and the effect of SUA on the signal pathway of muscle fiber type transformation.The results showed that:(1)After the intervention of GPR91 on the gastrocnemius muscle of mice,the effect of SUA on the transformation of muscle type and the activity of oxidative metabolism-related enzymes were reversed.(2)After interfering with GPR91 in C2C12 cells was same as in mice.(3)blocking PLC-? the downstream of GPR91 in C2C12 cells,reversing the effect of SUA on the transformation of muscle fiber type.In summary,SUA cuold promote slow-twitch muscle fibers formation,whic h may through the GPR91 receptor to activate its downs tream calcium signaling pathway to induce MEF2 a,NFAT expression and translocation.O n the other hand,SUA increased the expression of PGC-1? and NRF1,to promote mitochondrial biosynthesis.