Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation |
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Authors: | Ji Eun Du Young Ah You Eun Jin Kwon Soo Min Kim Jeongae Lee Ki Hwan Han Young Ju Kim |
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Affiliation: | 1.Department of Obstetrics and Gynecology and Ewha Medical Research Institute, College of Medicine, Ewha Womans University, Seoul 07985, Korea; (J.E.D.); (Y.A.Y.); (E.J.K.); (S.M.K.);2.Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 02792, Korea;3.Department of Anatomy, College of Medicine, Ewha Womans University, Seoul 07985, Korea; |
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Abstract: | Fetal programming implies that the maternal diet during pregnancy affects the long-term health of offspring. Although maternal diet influences metabolic disorders and non-alcoholic fatty liver disease in offspring, the hepatic mechanisms related to metabolites are still unknown. Here, we investigated the maternal diet-related alterations in metabolites and the biological pathway in male offspring at three months of age. Pregnant rats were exposed to 50% food restriction during the prenatal period or a 45% high-fat diet during the prenatal and postnatal periods. The male offspring exposed to food restriction and high-fat diets had lower birth weights than controls, but had a catch-up growth spurt at three months of age. Hepatic taurine levels decreased in both groups compared to controls. The decreased hepatic taurine levels in offspring affected excessive lipid accumulation through changes in hepatocyte nuclear factor 4 A methylation. Moreover, the alteration of gluconeogenesis in offspring exposed to food restriction was observed to a similar extent as that of offspring exposed to a high fat diet. These results indicate that maternal diet affects the dysregulation in hepatic metabolism through changes in taurine levels and HNF4A methylation, and predisposes the offspring to Type 2 diabetes and non-alcoholic fatty liver disease in later life. |
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Keywords: | fetal programming food restriction high fat diet taurine HNF4A methylation |
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