LAUSR

Objectives It is now clear that non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has a developmental origin. Thus, we aims on to evaluate if a maternal diet intervention before pregnancy would be beneficial to reduce the risk for offspring NAFLD. Methods In our study, female mice were either on an NF diet (NF group), or a HF diet (HF group), for 9 weeks and continued on such diet through pregnancy and gestation, or switched from the 9-week HF to an NF diet for 1 week (H1N group) or 9 weeks (H9N group) before pregnancy. After weaning, the male offspring were given the HF diet for 12 weeks to promote NAFLD. Results Comparing to the NF offspring, the H1N and HF but not the H9N offspring, displayed more severe hepatic steatosis and glucose intolerance. More specifically, the H1N and HF offspring had abnormal blood lipid panel and abnormal free fatty acid composition in liver, while the H9N offspring displayed normal. These physiological changes were associated with a desensitized hepatic insulin/AKT signaling, an increased expression of genes and proteins for de novo lipogenesis, a decreased expression of genes and proteins for fatty acid oxidation, increased Pcsk9 expression and the AMPK signaling hypoactivation in the HF and H1N offspring. However, these effects were either completely or partially avoided in the H9N offspring. Conclusions In summary, we showed that an early maternal diet intervention is efficient to reduce the risk for offspring NAFLD caused by the maternal HF diet. These information will provide significant support for setting up guidelines that women at childbearing age could follow to select the ideal diets, prior to and during pregnancy, which not only immediately benefit the pregnant outcome but also give a long-term beneficial effect on offspring health. Funding Sources This project is supported by grants from the National Institutes of Health (NIDDK 1R01DK112368-01 to LX and KZ) and the USDA National Institute of Food and Agriculture, [Hatch] project [1010406] to LX.