Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter and elevating genomic methylation in mice fed a high-fat diet |
| |
| Institution: | 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;1. School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia;2. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia;3. Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia;4. Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children''s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA;5. Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA, USA;6. School of Surgery, University of Western Australia, Perth, Australia;1. Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busandaehak-ro, 63 Beon-gil, Geumjeong-gu, Busan 46241, Republic of Korea;2. Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229, USA;3. Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), 70 Cheomdan-ro, Dong-gu, Daegu 41062, Republic of Korea;1. UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Malaga, Malaga, Spain;2. CIBER of the Instituto de Salud Carlos III (CIBERDEM CB07/08/0019), Málaga, Spain;3. ECAI de Genomica del Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain |
| |
| 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 PPARα, 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: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
