Gestational High Fat Diet Programs Hepatic Gluconeogenic Gene Expression And Histone Modification In Offspring Rats

According to current CDC figures, diabetes rates continue to rise, but the mechanisms behind the in‐utero programming of diabetes development are unclear. It has been reported that a maternal high‐fat (HF) diet affects fetal liver development, which can lead to altered glucose metabolism in adulthood. In the current study, Obesity Resistant (OR) dams were fed a control (C) or a high‐fat (HF) diet during gestation. After cesarean delivery, offspring livers were analyzed to determine the consequences of a maternal HF diet on molecular markers of gluconeogenesis. We demonstrated that while HF‐fed dams were not heavier at the end of gestation and did not gain more gestational weight than C dams, HF offspring were heavier and had higher blood glucose at birth than C offspring. Liver mRNA analysis demonstrated that while maternal gluconeogenic genes were not affected by the HF diet, offspring of HF‐fed dams had significantly higher expression of hepatic G6Pase, Srebp1c, Cebpα, Pgc1a, and Pck1 , which also had an increased transcription rate. Pck1 ChIP analysis showed that a gestational HF diet resulted in epigenetic modifications of the histone code in offspring livers. Our results demonstrate that in‐utero exposure to HF diet has the potential to program the gluconeogenic capacity of offspring through epigenetic modifications, which could inevitably lead to altered insulin sensitivity in adulthood. Grant Funding Source : USDA