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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.

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


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.


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

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