Effect of high-fat diet prior to pregnancy on hepatic gene expression and histology in mouse offspring.

Maternal overnutrition and obesity are associated with fetal development and cause long-term effects in offspring. However, the effects of a high-fat diet specific to the pre-pregnancy period are not determined. The present study aimed to examine the effect of high-fat diet prior to pregnancy on the liver of mouse offspring. Female C57BL/6J mice were fed a normal chow (15.2% fat by energy) [control diet (CTR) and CTR pre-pregnancy (PP) groups] or a high-fat chow (31.2% fat by energy) [high-fat diet (HFD) and HFD-pre-pregnancy (PP) groups] for 3-4 weeks and then mated with male C57BL/6J mice fed normal chow. Some mothers continued on the same diet until pups reached 21 days of age (CTR and HFD), and others were fed the different chows from gestational day 0 (CTR-PP and HFD-PP) to determine the effects of a high-fat diet during the pre-pregnancy period in HFD-PP/CTR and HFD/CTR-PP comparisons. Liver tissues from pups were subjected to gene expression analysis by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and microarray, and histological analysis using Oil Red O staining (Sigma Chemical Co., Ltd., Balcatta, WA, USA). Lipid droplets were increased in hepatocytes of mice in HFD-PP compared to CTR and those in HFD compared to CTR-PP. Expression of stearoyl-coenzyme A desaturase 1 (Scd1), acetyl-coenzyme A carboxylase beta (Acacb), and fatty acid binding protein 5 (Fabp5) was increased by maternal high-fat diet during pre-pregnancy. The results showed that maternal high-fat diet intake prior to pregnancy uniquely affects metabolic phenotype related to health and disease in the liver of the next generation.