Dynamic Changes In Genes Related To Glucose Uptake And Utilization During Pig Skeletal And Cardiac Muscle Development

In the present study, we used pig as a model to investigate gene expression changes related to glucose uptake capacity and utilization in skeletal and cardiac muscles at different stages of development. We measured expression of 30 mRNA and 10 miRNAs which related to glucose uptake and utilization at 5 different time stages from embryonic day 90 to 7 years old in cardiac, longissimus doris muscle and psoas major muscle. Then, we performed bioinformatics analysis to uncover the dynamic changes in genes related to glucose uptake and utilization during pig skeletal and cardiac muscle development and the differentation among the cardiac, longissimus doris muscle and psoas major muscle from the transcription level. Furthermore, we performed correlation analysis between mRNA and miRNAs to uncover cooperative roles in glucose metabolism of skeletal and cardiac muscles.Results of mRNA expression showed that the expression pattern of mRNA were tissue differential. Genes in enriched expression pattern (P<0.05) were an age-dependent increase in cardiac and longissimus doris muscle from embryonic 90 days to 7 years old, while in psoas major muscle firstly up-regulated until 30 days or 180 days postnatally, and then down-regulated.Analysis of biological process enrichment of genes in enriched expression pattern showed that processes of glycolysis, glycogen biosynthesis, and transmembrane transport were enriched in cardiac muscle, suggesting the capacity of glucose uptake and utilization was increased in cardiac muscle during development. Processes of glycogenesis, transmembrane transport and phosphate metabolic were enriched in longissimus doris muscle, which indicate the capacity of glucose uptake and utilization was also increased in longissimus doris muscle. Processes related to oxidation and ATP synthesis were mainly enriched in psoas major muscle, indicating ATP generation from glucose aerobic oxidation were increased from embryonic 90 days to 30 days postnatally, and then down-regulated.Results of miRNA expression showed that the expression of miRNAs in enriched expression pattern of (P<0.05) in three muscle types were negatively from embryonic 90 days to 7 years old.The correlation analysis between microRNAs and mRNAs in three muscle types across different stages of development found that 43 pairs of potential microRNA-mRNA involved in regulating glucose metabolism. Of these potential miRNA-mRNA pairs, target prediction found three miRNA-mRNA target relationship, PFKM and miR-320, PI3K and miR-126,MAPK and miR-24, which were in validated by previous studies.The key genes TPI1, PFKM and MCT-4 which related to glycolysis process were highly expressed in longissimus doris muscle compared with cardiac muscle and psoas major muscle across the five age stages, while oxidation-related genes CS, PDH and ATPase-β were strongly up-regulated in psoas major muscle compared with longissimus doris muscle and cardiac muscle.Our results showed the dynamic changes of glucose uptake and utilization during pig development from gene transcription level, which provided evidences for further studies of energy metabolism, and accumulated basic data for pig as an animal model to study human diseases such as obesity, diabetes and its complications.