Oxaloacetate Regulate Skeletal Muscle Energy Metabolism Via JNK Inflammation Signaling Pathway

Skeletal muscle is the largest organ in animals,which accounts for about 40%of the weight of adult animals.Skeletal muscle plays a key role in muscle growth and development,maintaining blood glucose and function of exercise.The mitochondria are main organelle of metabolism in the skeletal muscle cells.They are responsible for various metabolic pathways such as lipids metabolism,amino acids metabolism,The tricarboxylic acid cycle and urea cycle,etc.The TCA cycle is an important centre for the metabolism of the three major substance metabolisms.In recent years,studies have shown that in addition to supplying energy,mitochondrial tricarboxylic acid intermediates also have a variety of complex signaling molecular functions.However,there are currently few reports about the physiological effects of oxaloacetate,and the regulation of oxaloacetate on skeletal muscle metabolism is still unknow.In this paper,46 4-week-old C57BL/6J male mice were randomly divided into 5 groupes according to body weight.1% oxaloacetate were added to the diet for oxaloacetate treatment group(Malic acid,citric acid and aspartic acid were also used as controls).The body weight,food intake and body composition data were recorded.Before the end of the experiment,the whole-body metabolic rate of the mouse,and analyze the muscle grip,low intensity treadmill exercise and muscle contraction performance were tested.Meanwhile,after collecting Gastrocnemius muscle,muscle fiber type and diameter were tested via ATPase staining;and related metabolic indicators in skeletal muscle were tested such as glycogen,phosphocreatine,Adenosine triphosphate and free fatty acid,etc.;collect samples of blood to test glucose and non-esterified fatty acids content.Finally,GAS Mitochondrial uncoupling protein 2specific knockout mice and whole body c-Jun N-terminal kinase-inhibited mice were obtained via GAS UCP2 specific knockout and injection of SP600125 to inhibit JNK to study the mechanism of UCP2 and JNK-mediated oxaloacetate regulating skeletal muscle energy metabolism.The results showed that:(1)1% oxaloacetate can significantly reduce the exercise performance of mice and the fatigue time of GAS by adding in chow diet.(2)1% oxaloacetate has no significant effect on growth performance,body composition,muscle fiber type and diameter by adding in chow diet.(3)1% oxaloacetate significantly increased the energy consumption of mice during day and night time,the respiratory entropy of the mice during the day time and reduced the muscle glycogen reserve.(4)After specific knockout of UCP2 in the GAS muscle,the effect of oxaloacetate on reducing the exercise performance of mice was relieved,and the depletion of energy substrate in GAS muscle was reversed.(5)After injecting SP600125 to inhibit JNK,it reversed the effect of oxaloacetate on reducing the exercise performance and reversed the depletion of phosphocreatine(PCr)in the GAS muscle.In summary,oxaloacetate can reduce muscle glycogen content and accelerate the depletion of energy substrate via JNK inflammation signaling pathway and UCP2,thereby reducing the animal’s exercise ability.The results are of great significance for understanding the regulation of oxaloacetate for skeletal muscle energy metabolism and provide a new strategy for the nutritional regulation of muscle glycogen metabolism.