Postnatal High-Fat Diet Increases Liver Steatosis and Apoptosis Threatened by Prenatal Dexamethasone through the Oxidative Effect.

The objective of this study was to investigate cellular apoptosis in prenatal glucocorticoid overexposure and a postnatal high fat diet in rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered saline (vehicle) or dexamethasone and weaned onto either a normal fat diet or a high fat diet for 180 days; in total four experimental groups were designated, i.e., vehicle treated group (VEH), dexamethasone treated group (DEX), vehicle treated plus high-fat diet (VHF), and dexamethasone treated plus high-fat diet (DHF). Chronic effects of prenatal liver programming were assessed at postnatal day 180. The apoptotic pathways involved proteins were analyzed by Western blotting for their expressions. Apoptosis and liver steatosis were also examined by histology. We found that liver steatosis and apoptosis were increased in the DHF, DEX, and VHF treated groups, and that the DHF treated group was increased at higher levels than the DEX and VHF treated groups. The expression of leptin was decreased more in the DHF treated group than in the DEX and VHF treated groups. Decreased peroxisome proliferator-activated receptor-gamma coactivator 1α, phosphoinositide-3-kinase, manganese superoxide dismutase and increased malondialdehyde expression levels were seen in DHF treated group relative to the DEX treated group. The DHF treated group exhibited higher levels of oxidative stress, apoptosis and liver steatosis than the DEX treated group. These results indicate that the environment of high-fat diet plays an important role in the development of liver injury after prenatal stress.

Melatonin in the regulation of liver steatosis following prenatal glucocorticoid exposure.

Nonalcoholic fatty liver disease patients are characterized by hepatic steatosis. Prenatal glucocorticoid overexposure can result in steatosis. In this study, we aimed to determine the mechanism and cellular apoptosis of prenatal glucocorticoid overexposure in rats and whether melatonin can rescue the prenatal glucocorticoid-induced steatosis and apoptosis in neonatal rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered dexamethasone. Acute effects of prenatal programming liver were assessed at postnatal day 7. The expression of proteins involved in the apoptotic and methylation pathways was analyzed by RT-PCR and Western blotting. Apoptosis and steatosis were examined by histology staining. The liver steatosis and apoptosis were increased in prenatal glucocorticoid group more than in control group and decreased in melatonin group. The expression of leptin decreased in prenatal glucocorticoid and increased in melatonin group by liver RT-PCR and Western blot study. Caspase 3, TNF- α proteins expression, and TUNEL stains increased in prenatal glucocorticoid compared with control and decreased in melatonin group. The liver histone deacetylase, DNA methyltransferase activity, and DNA methylation were increased in prenatal glucocorticoid and decreased in melatonin group. The present study showed that the prenatal glucocorticoid induced programming liver steatosis at day 7 after delivery, possibly via altered leptin expression. Melatonin can reverse the methylation of leptin and decreased liver steatosis.