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Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

by Demin Cai 1,†, Mengjie Yuan 1,†, Haoyu Liu 2,†, Shifeng Pan 1, Wenqiang Ma 1, Jian Hong 1 and Ruqian Zhao 1,3,*
1
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
2
Department of Medical Cell Biology, Uppsala University, Uppsala SE-75123, Sweden
3
Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing 210095, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Nutrients 2016, 8(10), 646; https://doi.org/10.3390/nu8100646
Received: 15 August 2016 / Revised: 20 September 2016 / Accepted: 2 October 2016 / Published: 18 October 2016
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 hepatic S-adenosylmethionine (SAM) and S-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. View Full-Text
Keywords: betaine; AMPK; LXR; cholesterol metabolism; maternal diet; piglets betaine; AMPK; LXR; cholesterol metabolism; maternal diet; piglets
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Cai, D.; Yuan, M.; Liu, H.; Pan, S.; Ma, W.; Hong, J.; Zhao, R. Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification. Nutrients 2016, 8, 646.

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