Programming of phosphoenolpyruvate carboxykinase by maternal high fat diet may contribute to hepatic fat accumulation in female offspring rats (942.6)

Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) produces phosphoenolpyruvate during glyceroneogenesis. We previously demonstrated that high fat diet during pregnancy induced PEPCK mRNA expression in neonatal pups, which is characterized by histone modifications in specific regions of the gene. In the present study, we investigated persistency of the alterations in adult offspring. Dams were fed either control or high fat diet throughout gestation and lactation. Offspring were placed on control diet after weaning, generating C/C and HF/C groups. Liver was collected at 12 wks of age. Hepatic NADH level was increased in both genders but fat accumulation occurred only in female liver (HF/C). This was accompanied by a significant increase of PEPCK and Fatty Acid Synthase (FASN) mRNA expression in female liver. The induction of PEPCK gene expression was associated with an increased dimethylated histone H3 lysine 4 level in multiple regions of the gene. Meanwhile, trimethylated histone H3 lysine 4 was induced at a specific coding region in HF/C, accompanied by a decreased trimethylated histone H3 lysine 9 level at the promoter. In conclusion, maternal high fat diet programs PEPCK expression through histone modifications in adult offspring. Persistent PEPCK induction contributes to triglyceride synthesis. Combined with induced FASN and NADH, this leads to increased fat deposition in a gender‐specific manner.