AUTHOR=Zhang Qian , Xiao Xinhua , Zheng Jia , Li Ming , Yu Miao , Ping Fan , Wang Tong , Wang Xiaojing 

TITLE=Maternal Inulin Supplementation Alters Hepatic DNA Methylation Profile and Improves Glucose Metabolism in Offspring Mice

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00070

DOI=10.3389/fphys.2020.00070

ISSN=1664-042X

ABSTRACT=<sec><title>Scope</title><p>As a prebiotic, inulin may have a protective effect on glucose metabolism. However, the mechanism of inulin treatment on glucose intolerance in offspring exposed to a maternal high-fat (HF) diet is still not clear. Here, we examined the hepatic DNA methylation profile to determine how maternal inulin supplementation modified glucose metabolism in offspring mice.</p></sec><sec><title>Procedures</title><p>Female mice were fed a HF diet, control diet (CON), or a HF diet with inulin supplementation (HF-inulin) during gestation and lactation. Upon weaning, pup livers were obtained. A hepatic genome DNA methylation array was performed.</p></sec><sec><title>Results</title><p>Pups exposed to a maternal HF diet exhibited glucose intolerance and insulin resistance. Maternal inulin treatment moderated glucose metabolism. A DNA methylation array identified differentially methylated regions associated with 970 annotated genes from pups exposed to a HF diet in response to maternal inulin treatment. In particular, the wingless-type MMTV integration site family member 5A (<italic>Wnt5a</italic>) gene was hypermethylated, and the phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (<italic>Pik3c2a</italic>), phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta (<italic>Pik3c2b</italic>), and phosphoinositide-3-kinase regulatory subunit 2 (<italic>Pik3r2</italic>) genes were hypomethylated in inulin-treated pups. Consistently, hepatic <italic>Wnt5a</italic> gene expression was reduced and <italic>Pik3c2a</italic>, <italic>Pik3c2b</italic>, and <italic>Pik3r2</italic> gene expression were increased in the inulin group.</p></sec><sec><title>Conclusion</title><p>Maternal inulin treatment improved glucose intolerance by changing DNA methylation and gene expression of <italic>Wnt5a</italic> and <italic>Pi3k</italic> in mice exposed to a maternal HF diet.</p></sec>