Nutritional mismatch in postnatal life of low birth weight rat offspring leads to increased phosphorylation of hepatic eukaryotic initiation factor 2 α in adulthood

Maternal Undernutrition and Long-Term Effects on Hepatic Function

“…Similar to uterine-ligated offspring, MPR offspring with catch-up growth have decreases in hepatic Igf-1; however, the decrease in Igf-1 is mainly attributed to the effects of protein restriction during lactation [63]. All in all, the MPR model truly reinforces the main principle of Barker's "predictive adaptive response" given that when there is no nutritional mismatch in postnatal life, MPR offspring do not exhibit any decreases in cholesterol catabolism, insulin sensitivity, or drug metabolism in the liver [34,64,72].…”

“…Therefore, the MPR model is a relevant model to study placental insufficiency-IUGR as it leads to asymmetric IUGR, without any effects on maternal weight gain or food intake [22,63]. Moreover, MPR offspring have decreases in fetal liver weight at birth and, depending on the timing of protein restoration, display liver and whole body catch-up growth despite no differences in food intake [34,64]. Remarkably, MPR offspring, more predominantly in males, exhibit several symptoms of the metabolic syndrome including glucose intolerance, visceral obesity, hypercholesterolemia, and hypertension [34,[65][66][67][68][69].…”

“…Remarkably, MPR offspring, more predominantly in males, exhibit several symptoms of the metabolic syndrome including glucose intolerance, visceral obesity, hypercholesterolemia, and hypertension [34,[65][66][67][68][69]. The glucose intolerance is attributed to augmented gluconeogenesis (e.g., G6Pase, 11β-HSD1), diminished glucokinase expression, decreased pAkt1 (Ser473), and decreased glucagon receptor in the livers of MPR offspring [64,67,70,71]. With respect to lipids, MPR male offspring with catch-up growth show increases in circulating hepatic cholesterol due to decreases in the expression of Cyp7a1, the critical enzyme in cholesterol metabolism [34].…”

“…In several animal models of maternal undernutrition leading to metabolic disease, often the changes in hepatic gene expression do not occur directly at the time of the perinatal insult but manifests later in life [58,64,72]. This may be attributed to long-term global changes (e.g., epigenetic mechanisms), initiated by the perinatal environment, which precedes the eventual alterations in gene function.…”

“…ER stress occurs when perturbation in the function or homeostasis of the ER leads to luminal accumulation of misfolded or unfolded proteins [64]. Many known triggers of ER stress include impaired disulfide bond formation, compromised Ca 2+ homeostasis, low amino acids, hypoxia, decreased N-linked glycosylation, increased lipid load, and greater oxidative stress.…”