title: Maternal betaine supplementation in rats induces intergenerational changes in hepatic IGF-1 expression and DNA methylation.
abstract: Betaine is widely used in animal nutrition to promote growth. Here, we aimed to investigate whether maternal betaine supplementation during pregnancy can exert multigenerational effects on growth across two generations and the possible epigenetic modifications associated to such effects.
  
  
  
  In this study, 3-month-old female Sprague-Dawley rats were fed diet supplemented with 1% betaine throughout the pregnancy and lactation. Betaine-supplemented dams produced bigger litter but smaller F1 pups at birth and weaning. However, F2 pubs had higher weaning weight. In accordance with the growth performance, serum insulin-like growth factor 1 (IGF-1) levels were significantly lower in F1 yet higher in F2 pups, so was hepatic IGF-1 mRNA expression. Concurrently, dietary betaine supplementation to F0 dams increased hepatic expression of betaine homocysteine methyltransferase, at both mRNA and protein levels, in F1, but not F2 pups. Moreover, hepatic IGF-1 gene promoter 1 was detected to be significantly hypermethylated in F1 pups, whereas both promoters 1 and 2, together with almost all exons, were found to be hypomethylated in F2 offspring.
  
  
  
  Maternal betaine supplementation during pregnancy and lactation exerts distinct effects on growth of F1 and F2 rat offspring, probably through differential modification of IGF-1 gene methylation and expression in liver.
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Dong
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.|Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing, P. R. China.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001622:Betaine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007774:Lactation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008715:Methionine / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D017207:Rats, Sprague-Dawley
chemical_list: C548904:insulin-like growth factor-1, rat; D001622:Betaine; D007334:Insulin-Like Growth Factor I; D008715:Methionine
keywords: Betaine; DNA methylation; F1 offspring; F2 offspring; IGF-1