Abstract
Fetal growth restriction (FGR) leads to adult-onset metabolic syndrome. Intrauterine and early postnatal caloric restriction ameliorates the risk in animal models. To understand the underlying mechanism, we compared autophagic marker levels between offspring with FGR and those with prenatal and early postnatal protein restriction (IPPR). We postulated that FGR would impair, whereas IPPR would help regulate, autophagy in neonatal rats. This study involved control (Con), FGR offspring (Pre), and IPPR offspring groups (Pre + Post); n = 5/group. We assessed the abundance of autophagy markers in the liver and skeletal muscles. At birth, the Pre group pups had lower levels of some autophagy-related proteins, with increased p62 expression and a low microtubule-associated protein light chain beta (LC3-II:LC3-I) ratio. This finding suggests a lower hepatic autophagy flux in FGR offspring than the Con group. The hepatic levels of autophagy proteins were considerably decreased in the Pre and Pre + Post groups at 21 days of age compared to the Con group, but the LC3-II:LC3-I ratio was higher in the Pre + Post group than in the Con and Pre groups. The muscle levels of beclin-1, LC3-II, and p62 were lower in the Pre group pups, with no difference in the LC3-II:LC3-I ratio among the groups. An imbalance in the nutritional environment is associated with downstream autophagic flux, thus suggesting that FGR offspring will have impaired autophagic flux, and that post-natal nutrition restriction might help reduce this risk.