Decreased abundance of eIF4F subunits predisposes low-birth-weight neonatal pigs to reduced muscle hypertrophy.

Muscle hypertrophy is limited in low-birth-weight (LBWT) neonates, suggesting a reduction in protein synthesis and increased protein degradation. Sixteen pairs of 1-d old normal-birth-weight (NBWT) and LBWT littermates (n = 16) were euthanized and the longissimus dorsi (LD) was sampled for protein abundance and kinase phosphorylation profiles measures. Eukaryotic initiation factor (eIF) 4E and eIF4G abundance, and assembly of the active eIF4E-eIF4G complex was less for LBWT than for NBWT pig muscles. Similarly, eIF3f abundance was reduced in muscle of LBWT compared with NBWT pig and was associated with diminished ribosomal protein S6 kinase 1 (S6K1) phosphorylation. This decrease was linked to a lower phosphorylation of programmed cell death protein 4 (PDCD4) in LBWT pig muscle. By contrast, PDCD4 abundance was greater in muscle of LBWT than NBWT group, suggesting lower release and availability of eIF4A from PDCD4-eIF4A complex. Moreover, protein abundance of eIF4A was lower in LBWT muscle, which is expected to further impair the formation of eIF4F translation initiation complex. Microtubule associated light chain 3 (LC3) II to total LC3 ratio was greater in LBWT LD lysates yet P62 abundance was similar between the two groups suggesting no difference in autophagy. Muscle atrophy F-box (atrogin-1) abundance was less in LBWT LD lysates, suggesting decreased degradation through the ubiquitin-proteasome system. In conclusion, limited eIF4F subunit abundance and downregulated translation initiation are plausible mechanisms for diminished muscle growth in LBWT compared with NBWT neonatal pigs.