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J Nutr Biochem. 2014 Mar;25(3):329-36. doi: 10.1016/j.jnutbio.2013.11.007. Epub 2013 Dec 3.

Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter and elevating genomic methylation in mice fed a high-fat diet.

Author information

1
Faculty of Nutrition, School of Public Health, Sun Yat-Sen University, 510080 Guangzhou, People's Republic of China.
2
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, University of Sun Yat-Sen, 510120 Guangzhou, People's Republic of China.
3
Research and Therapy Center for Liver Disease, the Affiliated Dongnan Hospital of Xiamen University, 363000 Zhangzhou, People's Republic of China.
4
Faculty of Nutrition, School of Public Health, Sun Yat-Sen University, 510080 Guangzhou, People's Republic of China. Electronic address: zhuhl@mail.sysu.edu.cn.

Abstract

Aberrant DNA methylation contributes to the abnormality of hepatic gene expression, one of the main factors in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Betaine is a methyl donor and has been considered to be a lipotropic agent. However, whether betaine supplementation improves NAFLD via its effect on the DNA methylation of specific genes and the genome has not been explored. Male C57BL/6 mice were fed either a control diet or high-fat diet (HFD) supplemented with 0%, 1% and 2% betaine in water (wt/vol) for 12 weeks. Betaine supplementation ameliorated HFD-induced hepatic steatosis in a dose-dependent manner. HFD up-regulated FAS and ACOX messenger RNA (mRNA) expression and down-regulated PPARĪ±, ApoB and MTTP mRNA expression; however, these alterations were reversed by betaine supplementation, except ApoB. MTTP mRNA expression was negatively correlated with the DNA methylation of its CpG sites at -184, -156, -63 and -60. Methylation of these CpG sites was lower in both the 1% and 2% betaine-supplemented groups than in the HFD group (averages; 25.55% and 14.33% vs. 30.13%). In addition, both 1% and 2% betaine supplementation significantly restored the methylation capacity [S-adenosylmethionine (SAM) concentration and SAM/S-adenosylhomocysteine ratios] and genomic methylation level, which had been decreased by HFD (0.37% and 0.47% vs. 0.25%). These results suggest that the regulation of aberrant DNA methylation by betaine might be a possible mechanism of the improvements in NAFLD upon betaine supplementation.

KEYWORDS:

Betaine; DNA methylation; Methylation capacity; Microsomal triglyceride transfer protein; Nonalcoholic fatty liver disease

PMID:
24456734
DOI:
10.1016/j.jnutbio.2013.11.007
[Indexed for MEDLINE]

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