Enhanced hepatic cholesterol accumulation induced by maternal betaine exposure is associated with hypermethylation of CY
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ORIGINAL ARTICLE
Enhanced hepatic cholesterol accumulation induced by maternal betaine exposure is associated with hypermethylation of CYP7A1 gene promoter Nannan Zhao1,2 Shu Yang1,2 Yue Feng1,2 Bo Sun1,2 Ruqian Zhao1,2 ●
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Received: 15 December 2018 / Accepted: 15 March 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose Betaine contains three methyl groups and plays a critical role in regulating glucose and lipid metabolism via epigenetic modifications. However, it is unclear whether prenatal betaine intake could affect cholesterol metabolism of progeny through DNA methylation. Methods Hence, pregnant rats were randomly divided into control and betaine groups fed standard diet or 1% betaine supplementation diet, respectively, throughout gestation and lactation. Results Maternal betaine exposure significantly (P < 0.05) increased serum and hepatic cholesterol contents but not triglyceride levels in offspring rats. Accordantly, maternal intake of betaine markedly downregulated (P < 0.05) hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) expression at both the mRNA and protein level, while the protein content of lowdensity lipoprotein receptor (LDLR) was upregulated in the liver of betaine-exposed rats. In addition, prenatal betaine supplementation extremely increased (P < 0.05) hepatic betaine-homocysteine methyltransferase (BHMT) expression at the mRNA and protein level but not affected the expression of other key enzymes involved in methionine metabolism. Furthermore, hepatic hypermethylation of CYP7A1 gene promoter was observed in progeny rats derived from betainesupplemented dams. Conclusions Our results provide evidence that maternal betaine supplementation significantly enhances hepatic cholesterol contents accompanied with alterations of cholesterol metabolic genes and hypermethylation in offspring rats at weaning. Keywords Maternal Betaine DNA methylation Cholesterol ●
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Introduction Cholesterol is an essential constituent of cell membranes and is required to maintain cell membrane integrity and fluidity [1]. Under normal condition, hepatic cholesterol homeostasis
Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-019-01906-z) contains supplementary material, which is available to authorized users. * Ruqian Zhao [email protected] 1
MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, 210095 Nanjing, P. R. China
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Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, 210095 Nanjing, P. R. China
plays a vital role in maintaining physiological process via converting into various hormones and bile acids [2]. However, abnormal cholesterol metabolism is associated with metabolic syndrome disease, such as cardiovascular diseases and nonalcoholic fatty liver disease (NAFLD) [3, 4]. Thus it is critical to maintain cholesterol homeostasis via biosynthesis, conversion, and transport. 3-Hydroxy-3-meth
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