Maternal diet intervention before pregnancy primes offspring lipid metabolism in liver

Abstract

Nonalcoholic fatty liver disease (NAFLD) has a developmental origin and is influenced in utero. We aimed to evaluate if maternal diet intervention before pregnancy would be beneficial to reduce the risk of offspring NAFLD. In our study, female mice were either on a normal-fat diet (NF group), or a high-fat diet for 12 weeks and continued on this diet throughout pregnancy and lactation (HF group), or switched from HF-to-NF diet 1 week (H1N group), or 9 weeks (H9N group) before pregnancy. Compared with the NF offspring, the H1N and HF, but not the H9N offspring, displayed more severe hepatic steatosis and glucose intolerance. More specifically, an abnormal blood lipid panel was seen in the H1N offspring and abnormal hepatic free fatty acid composition was present in both the HF and H1N offspring, while the H9N offspring displayed both at normal levels. These physiological changes were associated with desensitized hepatic insulin/AKT signaling, increased expression of genes and proteins for de novo lipogenesis and cholesterol synthesis, decreased expression of genes and proteins for fatty acid oxidation, increased Pcsk9 expression, and hypoactivation of 5′ AMP-activated protein kinase (AMPK) signaling in the HF and H1N offspring. However, these effects were completely or partially rescued in the H9N offspring. In summary, we found that early maternal diet intervention is effective in reducing the risk of offspring NAFLD caused by maternal HF diet. These findings provide significant support to develop effective diet intervention strategies and policies for prevention of obesity and NAFLD to promote optimal health outcomes for mothers and children.

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Acknowledgements

This project is supported by grants from the National Institutes of Health (NIDDK 1R01DK112368-01 to LX and KKZ). This work is supported by the USDA National Institute of Food and Agriculture, [Hatch] project [1010406] to LX. Portions of these studies were supported by a VA Merit Award, 4I01BX000574 to GA from the United States Department of Veteran’s affairs, the Hickam Endowed Chair Funds from Indiana University and the Strategic Research Initiative (SRI) from Indiana University Health, 41-855-96. The content is the responsibility of the author(s) alone and does not necessarily reflect the views or policies of the Department of Veterans Affairs or the United States Government.

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Correspondence to Linglin Xie.

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Zhou, Y., Peng, H., Xu, H. et al. Maternal diet intervention before pregnancy primes offspring lipid metabolism in liver. Lab Invest (2019). https://doi.org/10.1038/s41374-019-0344-4

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