NDLI: Maternal dietary betaine supplementation modifies hepatic expression of cholesterol metabolic genes via epigenetic mechanisms in newborn piglets.

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Maternal dietary betaine supplementation modifies hepatic expression of cholesterol metabolic genes via epigenetic mechanisms in newborn piglets.

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Maternal dietary betaine supplementation modifies hepatic expression of cholesterol metabolic genes via epigenetic mechanisms in newborn piglets.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cai, Demin Jia, Yimin Lu, Jingyu Yuan, Mengjie Sui, Shiyan Song, Haogang Zhao, Ruqian
Description	Author Affiliation: Cai D ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.); Jia Y ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.); Lu J ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.); Yuan M ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.); Sui S ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.); Song H ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.); Zhao R ( Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University,Nanjing210095,People's Republic of China.)
Abstract	To elucidate the effects of maternal dietary betaine supplementation on hepatic expression of cholesterol metabolic genes in newborn piglets and the involved epigenetic mechanisms, we fed gestational sows with control or betaine-supplemented diets (3 g/kg) throughout pregnancy. Neonatal piglets born to betaine-supplemented sows had higher serum methionine concentration and hepatic content of betaine, which was associated with significantly up-regulated hepatic expression of glycine N-methyltransferase. Prenatal betaine exposure increased hepatic cholesterol content and modified the hepatic expression of cholesterol metabolic genes in neonatal piglets. Sterol regulatory element-binding protein 2 was down-regulated at both mRNA and protein levels, while 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) was down-regulated at the mRNA level, but up-regulated at the protein level, in betaine-exposed piglets. The transcriptional repression of HMGCR was associated with CpG island hypermethylation and higher repressive histone mark H3K27me3 (histone H3 lysine 27 trimethylation) on the promoter, whereas increased HMGCR protein content was associated with significantly decreased expression of miR-497. Furthermore, LDL receptor was significantly down-regulated at both mRNA and protein levels in the liver of betaine-exposed piglets, which was associated with promoter CpG hypermethylation. In addition, the expression of cholesterol-27 -hydroxylase (CYP27 1) was up-regulated at both mRNA and protein levels, while the expression of cholesterol-7 -hydroxylase (CYP7 1) was increased at the mRNA level, but unchanged at the protein level associated with increased expression of miR-181. These results indicate that maternal betaine supplementation increases hepatic cholesterol content in neonatal piglets through epigenetic regulations of cholesterol metabolic genes, which involve alterations in DNA and histone methylation and in the expression of microRNA targeting these genes.
File Format	HTM / HTML
ISSN	00071145
Issue Number	9
Volume Number	112
e-ISSN	14752662
Journal	British Journal of Nutrition
Language	English
Publisher	Cambridge University Press (on behalf of The Nutrition Society)
Publisher Date	2014-11-14
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Nutritional Discipline Sciences Animals, Newborn Betaine Administration & Dosage Cholesterol Genetics Epigenesis, Genetic Drug Effects Liver Metabolism Sus Scrofa Animals Pharmacokinetics Bile Acids And Salts Blood Analysis Cholesterol 7-alpha-hydroxylase Dna Methylation Diet Veterinary Dietary Supplements Female Gene Expression Hydroxymethylglutaryl Coa Reductases Chemistry Male Maternal Nutritional Physiological Phenomena Methionine Micrornas Pregnancy Rna, Messenger Sterol Regulatory Element Binding Protein 2 Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Medicine

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