Liver Of Rat Offspring Research Articles

Proteomic Analysis of One-carbon Metabolism-related Marker in Liver of Rat Offspring

Maternal food intake has a significant effect on the fetal environment, and an inadequate maternal diet may result in intrauterine growth restriction. Intrauterine growth restriction newborn rat pups nursed by normal diet-fed dams exhibited rapid catch-up growth, which plays a critical role in the risk for metabolic and cardiovascular disease in later life. Specifically, one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. Data are available via ProteomeXchange with identifier PXD002578. We determined that betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p < 0.05). Moreover, the expression levels of betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial were negatively correlated with serum homocysteine concentration in male offspring exposed to maternal food restriction during gestation and normal diet during lactation. However, in female offspring only expression levels of methylenetetrahydrofolate dehydrogenase 1 were negatively correlated with homocysteine concentration. This study shows that maternal food restriction during late gestation and normal diet during lactation lead to increased homocysteine concentration through disturbance of one-carbon metabolism in the livers of male offspring. This suggests that male offspring have an increased gender-specific susceptibility to disease in later life through fetal programming.

Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring

We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance.Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR.Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression.In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

Early-Life Exposure to Bisphenol A Induces Liver Injury in Rats Involvement of Mitochondria-Mediated Apoptosis

Exposure to bisphenol A (BPA), a monomer widely used to manufacture polycarbonate plastics, has been reported to be associated with abnormalities of liver function and hepatic damage. However, the molecular mechanism under the pathogenesis of hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA at the reference dose of 50 µg/kg/day on the apoptotic index in the liver of rat offspring was investigated. Increased levels of ALT and enhanced cell apoptosis were observed in the liver of rat offspring at 15 and 21 weeks, and significantly increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c were also confirmed. In addition, significant change in the expression levels of Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For in vitro experiments, liver mitochondria were isolated from neonatal rats and were treated with BPA. BPA treatment led to a significant increase in mitochondrial permeability transition. Moreover, the supernatant from BPA-treated mitochondria significantly increased apoptotic changes in nuclei isolated from liver tissue. In conclusion, the study demonstrates that BPA induces mitochondria-mediated apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity induced by early-life exposure to BPA.

Ethanol in lactation promotes oxidative stress in different phases of rat offspring

Summary Backgroud & aims To evaluate the effect of ethanol on body weight and biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), and levels of lipoperoxidation (TBARS) in blood and liver of rat offspring. Methods Offspring ( n = 36) of adult Wistar rats in a Control Group (CG; n = 3) and in an Experimental Group (EG; n = 3) were randomized in phases of lactation, young and adult ( n = 6 rats/group). Controls received water ad libitum while EG received water with 20% ethanol during 12 days of lactation. Results Comparing EG to CG, there was lower weight gain in lactation and young ( p p = 0.018, p p p = 0.008, p = 0.008, p = 0.004, respectively) and adults ( p p = 0.017, p = 0.053, respectively) were found. Conclusions The maternal consumption of ethanol during lactation caused lower body weight gain in lactation and young offspring groups, normalizing in adults, as well as decreases in the activity of SOD in blood and in GST, GPx and CAT in liver of young and adults.