Early gestational maternal low-protein diet diminishes hepatic response to fasting in young adult male mice

Maternal low-protein (MLP) diet can lead to hepatic steatosis, which only develops with ageing. It is still unclear whether the young offspring show any signs of past exposure to prenatal adverse conditions. We hypothesized that early nutritional insult would first affect the dynamic responsiveness to nutritional challenges rather than the static state. We analyzed the transcriptome and metabolome profiles of the hepatic response to fasting/refeeding in young male mice offspring to identify changes induced by early gestational MLP diet. Restricted MLP exposure strictly to early gestation was achieved by the embryo transfer method. As a result, significant transcriptional differences between control and MLP pups were found only in the fasted state. The fasting-induced upregulation of genes for long-chain fatty acid metabolism and of stress response genes related to protein folding were significantly diminished in MLP pups. Gene Set Enrichment Analysis showed that peroxisome proliferator activated receptor  (PPAR)-mediated induction was impaired in fasted MLP pups. Lipid profiling showed that the hepatic signature of triacylglycerols was shifted to longer acyl-chains and higher saturation by the MLP diet. Taken together, early gestational MLP diet affected the hepatic dynamic response to nutritional stress in seemingly healthy young offspring, accompanied with partial deterioration of PPAR action. This study tested whether early gestational maternal low protein diet affects hepatic metabolism even in seemingly healthy young offspring. We subjected offspring to fasting stress to uncover difference in the dynamic hepatic response, caused by early gestational MLP diet. Liver RNA expression profiles were compared between Ctrl and MLP pups, at the three nutritional conditions (ad libitum fed, fasted and refed)