Dysfunction of Insulin-like Growth Factor Signaling in Skeletal Muscles of Low Birth Weight Neonatal Pigs

Low birth weight (LBWT) neonates experience restricted fetal muscle development and impaired postnatal muscle growth. Our previous data suggest that protein synthesis is lower while protein degradation is not different in skeletal muscle of LBWT compared to normal birth weight (NBWT) neonatal pigs. We hypothesized that decreased protein synthesis in skeletal muscle of LBWT pigs is a consequence of dysfunction of insulin‐like growth factor (IGF) signaling cascade. Twenty four LBWT and NBWT male pigs were euthanized to collect blood and longissimus dorsi (LD) muscle samples. Plasma IGF‐I concentration was measured using a commercial ELISA kit, mRNA expression by real‐time PCR and protein expression and phosphorylation by western blot. Plasma IGF‐I concentration and mRNA expression of IGF‐I and IGF binding protein 5 (IGFBP 5) were lower in LD muscle of LBWT pigs ( P < 0.05). However, mRNA and protein expression of IGF‐I receptor was higher in the LD muscle of LBWT compared to NBWT pigs ( P < 0.05). Protein expression of eukaryotic initiation factor 4E binding protein 1 (4EBP1) and phosphorylation of ribosomal protein S6 kinase 1 (S6K1) were lower in LD muscle of LBWT compared to their NBWT siblings ( P < 0.05). These results suggest that in spite of the increased abundance of IGF‐I receptor in muscles of LBWT pigs, there is a reduction in the expression of downstream effectors of IGF‐I. As a result, IGF signaling is compromised and could contribute to impaired postnatal muscle growth in LBWT compared to NBWT neonatal pigs. Support or Funding Information Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture (S.W. El‐Kadi)