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

Wang, Lijun; Zhang, Hongwei; Zhou, Jingya; Liu, Yan; Yang, Yang; Chen, Xiaoling; Zhu, Cui-hong; Zheng, Rongqin; Liu, Wenhua; Zhu, Huilian

doi:10.1016/j.jnutbio.2013.11.007

Cited by 109 publications

(90 citation statements)

References 40 publications

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“…These results were different from those in the experimental model of adult mice as they declared that betaine supplementation significantly decreased TG and cholesterol level [29,30]. However, other studies even found an elevation in plasma TG and cholesterol after betaine supplementation [25,31].…”

Section: Discussionmentioning

confidence: 62%

“…In addition, studies also suggested that the effects of betaine on hepatic lipid deposition might also be through its ability to increase endogenous carnitine, as carnitine might increase carnitine palmitoyltransferase I-mediated fatty acid translocation into the mitochondria and β-oxidation [6,22]. Recently, the effects of betaine on the rectification of DNA methylation have also been declared to be a major mechanism accounting for the hepatoprotective effects of betaine [9,30]. These effects of betaine were mostly due to its role in one-carbon metabolism as a methyl donor.…”

Section: Discussionmentioning

confidence: 99%

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FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Chen

Zhou

et al. 2015

J Physiol Biochem

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Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m(6)A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m(6)A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m(6)A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Chen

Zhou

et al. 2015

J Physiol Biochem

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show abstract

“…On the other hand, the myocardial levels of betaine were significantly higher in KO mice heart than in WT mice heart. Recently, it has been reported that betaine supplementation improved hepatic steatosis in both nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver through down-regulation of lipogenic genes and up-regulation of fatty acid oxidation genes [36,37]. The expressions of fatty acid oxidation genes, LCAD and MCAD, were not increased in KO mice heart ( Figure 4A).…”

Section: Accepted Manuscriptmentioning

confidence: 93%

Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice

et al. 2015

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“…This may reflect the normal high rate of betaine consumption through the BHMT pathway because consumption must be reduced in order to conserve enough betaine to fulfill its osmolyte role in cell volume regulation. If abnormal hepatic gene expression is a major factor underlying development and progression of fatty liver disease [93], then BHMT could occupy a central role for alleviating the problem by supplying one-carbon units from betaine for methylation of specific genes. If this is true then species differences in BHMT affinity for betaine might account in part for the apparent failure of betaine supplements to improve liver injury in humans.…”

Section: Application To Liver Injury In Humansmentioning

confidence: 99%

Betaine chemistry, roles, and potential use in liver disease

Day

Kempson

2016

Biochimica et Biophysica Acta (BBA) - General Subjects

176

128

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

Cited by 109 publications

References 40 publications

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice

Betaine chemistry, roles, and potential use in liver disease

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