期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 64, 期 40, 页码 7530-7539出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.6b03615
关键词
cholesterol; DNA methylation; HMB; microRNA; nursery piglets
资金
- Feed Additive Safety Evaluation Program of the Ministry of Agriculture, China
- Jiangsu Natural Science Foundation of China [SBK2014043978]
- Fundamental Research Funds for the Central Universities [KYZ201212]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
Excess 2-hydroxy-(4-methylthio)butanoic acid (HMB) supplementation induces hyperhomocysteinemia, which contributes to hepatic cholesterol accumulation. However, it is unclear whether and how high levels of HMB break hepatic cholesterol homeostasis in nursery piglets. In this study, HMB oversupplementation suppressed food intake and decreased body weight in nursery piglets. Hyperhomocysteinemia and higher hepatic cholesterol accumulation were observed in HMB groups. Accordingly, HMB significantly increased the protein content of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and glycine N-methyltransferase (GNMT) but decreased that of aryl-coenzyme A:cholesterol acyltransferase-1 (ACAT1). Significant downregulation of miR-150, miR-181d-Sp, and miR-296-3p targeting the 3'-untranslated regions (UTRs) of GNMT and HMGCR was detected in the liver of HMB-treated piglets, and their functional validation was confirmed by dual-luciferase reporter assay. Furthermore, hypermethylation of miR-150 promoter was detected in association with suppressed miR-150 expression in the livers of HMB-treated piglets. This study indicated a new mechanism of hepatic cholesterol unhomeostasis by dietary methyl donor supplementation.
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