title: Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification.
abstract: Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepaticS-adenosylmethionine (SAM) andS-adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring.
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China. yzu.jsnj.ice@163.com.
authors.forename: Demin
authors.initials: D
authors.lastname: Cai
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China. senrutoday@163.com.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala SE-75123, Sweden. haoyu.liu@mcb.uu.se.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China. pan.sf@163.com.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Pan
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China. wq8110@126.com.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Ma
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China. jian_hong602@sina.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China. zhao.ruqian@gmail.com.|Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing 210095, China. zhao.ruqian@gmail.com.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001622:Betaine / Q000097:blood / Q000494:pharmacology*; D001942:Breast Feeding; D002784:Cholesterol / Q000097:blood / Q000235:genetics*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D019175:DNA Methylation; D019587:Dietary Supplements; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D042421:Histone Code; D006657:Histones; D007774:Lactation; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D011401:Promoter Regions, Genetic; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D013552:Swine; D014886:Weaning
chemical_list: D006657:Histones; D000071518:Liver X Receptors; D051122:Scavenger Receptors, Class B; D001622:Betaine; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D055372:AMP-Activated Protein Kinases
keywords: AMPK; LXR; betaine; cholesterol metabolism; maternal diet; piglets