title: Prenatal betaine exposure alleviates corticosterone-induced inhibition of CYP27A1 expression in the liver of juvenile chickens associated with its promoter DNA methylation.
abstract: Sterol 27-hydroxylase (CYP27A1) plays an important role in cholesterol homeostasis by degrading cholesterol to bile acids. Betaine can alleviate high-fat diet-induced hepatic cholesterol accumulation and maternal betaine treatment programs the hepatic expression of CYP27A1 in offspring. Excessive corticosterone (CORT) exposure causes hepatic cholesterol deposition in chickens, yet it remains unknown whether prenatal betaine modulates CORT-induced cholesterol accumulation in chicken liver later in life and whether it involves epigenetic gene regulation of CYP27A1. In this study, fertilized eggs were injected with saline or betaine at 2.5mg/egg before incubation, and the hatchlings were raised under the same condition till 56days of age followed by 7days of subcutaneous CORT injection. Plasma concentrations of total cholesterol (Tch), HDL- and LDL-cholesterol were significantly increased (P<0.05), after CORT challenge, in both control and betaine groups. However, prenatal betaine exposure prevented CORT-induced increase (P<0.05) in hepatic Tch content. Hepatic expression of cholesterol biosynthesis genes and ACAT1 protein that esterifies cholesterol for storage, were activated in both control and betaine groups upon CORT challenge. However, betaine-treated chickens were protected from CORT-induced repression (P<0.05) in LXR and CYP27A1 expression in the liver. CORT-induced down-regulation of LXR and CYP27A1 coincided with significantly increased (P<0.05) CpG methylation on their promoters, which was significantly ameliorated in betaine-treated chickens. These results suggest that in ovo betaine injection alleviates CORT-induced hepatic cholesterol deposition most probably through epigenetic regulation of CYP27A1 and LXR genes in juvenile chickens.
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Qinwei
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Abdulrahman A
authors.initials: AA
authors.lastname: Idriss
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Nagmeldin A
authors.initials: NA
authors.lastname: Omer
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, PR China; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, Nanjing 210095, PR China. Electronic address: zhao.ruqian@gmail.com.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001622:Betaine / Q000008:administration & dosage*; D015153:Blotting, Western; D002645:Chickens / Q000254:growth & development / Q000378:metabolism; D053493:Cholestanetriol 26-Monooxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D047468:Immunoprecipitation; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D001622:Betaine; D002784:Cholesterol; D053493:Cholestanetriol 26-Monooxygenase; D003345:Corticosterone
keywords: Betaine; CYP27A1; Cholesterol; Corticosterone; DNA methylation