title: In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.
abstract: Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations.
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Yun
authors: Y
authors: Hu
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Qinwei
authors: Q
authors: Sun
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Xiaoliang
authors: X
authors: Li
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Min
authors: M
authors: Wang
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Demin
authors: D
authors: Cai
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Xi
authors: X
authors: Li
authors: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Ruqian
authors: R
authors: Zhao
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001622:Betaine / Q000494:pharmacology*; D001835:Body Weight; D002645:Chickens / Q000254:growth & development / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010063:Ovum / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D006657:Histones; D012333:RNA, Messenger; D051782:Sterol Regulatory Element Binding Protein 2; D001622:Betaine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase