High nutrient intake alters muscular growth and metabolic status of neonatal intra-uterine growth-retarded pigs

Abstract Text: Intra-uterine growth-retarded (IUGR) neonates have shown an impairment of postnatal skeletal muscle morphology and function. We hypothesized that the growth and development of skeletal muscle of IUGR neonates might be affected by increased nutrient intake during the suckling period. Therefore, we investigated the effects of high nutrient intake (HNI) on the muscular growth and metabolic status of IUGR and normal-birth weight (NBW) piglets. Piglets with a birth weight near the mean litter birth weight (within 0.5 SD) were identified as NBW, whereas those at least 1.5 SD lower birth weight were defined as IUGR. A total of twelve pairs of IUGR and NBW piglets (7 d old) were randomly assigned to two different nutrient-level formula milk groups. After 21 d of rearing, muscle weight and morphology, activities of energy metabolism-related enzymes and muscle protein deposition-related genes involved in the insulin-like growth factor 1/Ak thymoma/mammalian target of rapamycin pathway were determined. The results indicated that semitendinosus and psoas major muscle weights were lighter (-31.7%~37.3%, p<0.001) in IUGR piglets, whereas HNI significantly increased psoas major muscle weight (+31.3%, p<0.001) and length (+17.6%, p=0.006). Likewise, IUGR decreased the cross-sectional areas (-26.4%~40.0%, p=0.002) and myofiber numbers (-20.8%~23.8%, p=0.004) of semitendinosus and psoas major muscle. Furthermore, IUGR piglets with HNI exhibited more myofibers (+25.7%, p<0.001) than those counterpart IUGR piglets, and these alterations in the muscle growth traits of IUGR piglets receiving HNI were accompanied by increasing muscular gene expressions of insulin-like growth factor 1 (+49.0%, p=0.003), insulin-like growth factor 1 receptor (+56.9%, p<0.001), Ak thymoma (+60.8%, p=0.002), mammalian target of rapamycin (+55.4%, p<0.001), ribosomal protein s6 (+78.6%, p=0.003), eukaryotic translation initiation factor 4E (+75.0%, p=0.002) that are related to muscle protein deposition. Otherwise, IUGR decreased lactate dehydrogenase activity (-13.1%, p=0.015) and activity ratios (-23.0%~26.9%, p<0.001) of lactate dehydrogenase: citrate synthase and lactate dehydrogenase: beta-hydroxy-acyl-CoA dehydrogenase, but increased beta-hydroxy-acyl-CoA dehydrogenase activity (+16.2%, p=0.023) in longissimus dorsi muscle. Inversely, HNI increased lactate dehydrogenase activity (+14.1%, p=0.021) and activity ratios (+21.8%~39.1%, p=0.004) of lactate dehydrogenase: citrate synthase and lactate dehydrogenase: beta-hydroxy-acyl-CoA dehydrogenase, but decreased beta-hydroxy-acyl-CoA dehydrogenase activity (-17.1%, p=0.006). In conclusion, the present findings suggest that increased nutrient intake during the suckling period altered muscular metabolic status and improved skeletal muscle growth possibly via regulation of insulin-like growth factor 1/Ak thymoma/mammalian target of rapamycin signaling pathway.

Keywords: Intra-uterine growth-retarded pigs: Nutrient intake: Skeletal muscle