Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD

Lai, Zhi-Wei; Chen, Junliang; Ding, Chenghe; Wong, Kwanshu; Chen, Xingyi; Pu, Liuzhen; Huang, Qiangwei; Chen, Xiaolin; Cheng, Ziyang; Liu, Yan; Tan, Xuying; Zhu, Huilian; Wang, Lijun

doi:10.1002/oby.22667

Cited by 30 publications

(30 citation statements)

References 43 publications

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“…100 Elevated serum Hcy concentrations are related to the histological severity of NAFLD. 101 However, high serum Hcy levels are negatively associated with NASH, and significant fibrosis in patients with NAFLD. The pathophysiological mechanisms between Hcy and NAFLD are multifactorial, and not fully understood.…”

Section: Methionine Metabolism and Cldsmentioning

confidence: 99%

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Wang

Liang

et al. 2020

Sig Transduct Target Ther

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As one of the bicyclic metabolic pathways of one-carbon metabolism, methionine metabolism is the pivot linking the folate cycle to the transsulfuration pathway. In addition to being a precursor for glutathione synthesis, and the principal methyl donor for nucleic acid, phospholipid, histone, biogenic amine, and protein methylation, methionine metabolites can participate in polyamine synthesis. Methionine metabolism disorder can aggravate the damage in the pathological state of a disease. In the occurrence and development of chronic liver diseases (CLDs), changes in various components involved in methionine metabolism can affect the pathological state through various mechanisms. A methionine-deficient diet is commonly used for building CLD models. The conversion of key enzymes of methionine metabolism methionine adenosyltransferase (MAT) 1 A and MAT2A/MAT2B is closely related to fibrosis and hepatocellular carcinoma. In vivo and in vitro experiments have shown that by intervening related enzymes or downstream metabolites to interfere with methionine metabolism, the liver injuries could be reduced. Recently, methionine supplementation has gradually attracted the attention of many clinical researchers. Most researchers agree that adequate methionine supplementation can help reduce liver damage. Retrospective analysis of recently conducted relevant studies is of profound significance. This paper reviews the latest achievements related to methionine metabolism and CLD, from molecular mechanisms to clinical research, and provides some insights into the future direction of basic and clinical research.

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Section: Methionine Metabolism and Cldsmentioning

confidence: 99%

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Wang

Liang

et al. 2020

Sig Transduct Target Ther

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“…The absence of considerable change in telomere length in our models indicates that telomere shortening is not involved in NAFLD development in the models used herein, implying that the emergence of NAFLD in non-aged organisms does not correlate with changes in telomere length. In NAFLD, data from both mouse and human studies propose an inverse correlation between global DNA methylation and disease progression [33,34]. In this context, changes in the methylation status of specific steatosis-related genes are considered of importance [35].…”

Section: Discussionmentioning

confidence: 99%

Hepatic Senescence Accompanies the Development of NAFLD in Non-Aged Mice Independently of Obesity

Moustakas

Κατσαρού

Legaki

et al. 2021

IJMS

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Senescence is considered to be a cardinal player in several chronic inflammatory and metabolic pathologies. The two dominant mechanisms of senescence include replicative senescence, predominantly depending on age-induced telomere shortening, and stress-induced senescence, triggered by external or intracellular harmful stimuli. Recent data indicate that hepatocyte senescence is involved in the development of nonalcoholic fatty liver disease (NAFLD). However, previous studies have mainly focused on age-related senescence during NAFLD, in the presence or absence of obesity, while information about whether the phenomenon is characterized by replicative or stress-induced senescence, especially in non-aged organisms, is scarce. Herein, we subjected young mice to two different diet-induced NAFLD models which differed in the presence of obesity. In both models, liver fat accumulation and increased hepatic mRNA expression of steatosis-related genes were accompanied by hepatic senescence, indicated by the increased expression of senescence-associated genes and the presence of a robust hybrid histo-/immunochemical senescence-specific staining in the liver. Surprisingly, telomere length and global DNA methylation did not differ between the steatotic and the control livers, while malondialdehyde, a marker of oxidative stress, was upregulated in the mouse NAFLD livers. These findings suggest that senescence accompanies NAFLD emergence, even in non-aged organisms, and highlight the role of stress-induced senescence during steatosis development independently of obesity.

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“…These studies indicate that HBV exposure contributes to a decrease in global DNA methylation and a subsequent increase in the risk of developing HCC. Findings from our laboratory and others have shown that the NAFLD and HCC patients have lower levels of global DNA methylation than corresponding controls (Wu et al, 2012;Nishida et al, 2013;Wang et al, 2014;Lai et al, 2020). However, whether the co-occurrence of CHB with NAFLD further aggravates global DNA hypomethylation in NAFLD patients has not been evaluated.…”

Section: Introductionmentioning

confidence: 86%

The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease

Lai

et al. 2021

Front. Genet.

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Global DNA hypomethylation has been reported in patients with chronic hepatitis B (CHB) and non-alcoholic fatty-liver disease (NAFLD). However, the global DNA methylation profile of patients with concurrent NAFLD and CHB (NAFLD + CHB) is still unclear. We aimed to detect the hepatic global DNA methylation levels of NAFLD + CHB patients and assess the associated risk factors. Liver biopsies were collected from 55 NAFLD patients with or without CHB. The histological characteristics of the biopsy were then assessed. Hepatic global DNA methylation levels were quantified by fluorometric method. The hepatic global DNA methylation levels in NAFLD + CHB group were significantly lower than that in NAFLD group. Participants with fibrosis showed lower levels of hepatic global DNA methylation than those without fibrosis. Participants with both CHB and fibrosis had lower levels of hepatic global DNA methylation than those without either CHB or fibrosis. The co-occurrence of CHB and fibrosis was significantly associated with a reduction in global DNA methylation levels compared to the absence of both CHB and fibrosis. Our study suggests that patients with NAFLD + CHB exhibited lower levels of global DNA methylation than patients who had NAFLD alone. The co-occurrence of CHB and liver fibrosis in NAFLD patients was associated with a decrease in global DNA methylation levels.

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Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD

Cited by 30 publications

References 43 publications

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Hepatic Senescence Accompanies the Development of NAFLD in Non-Aged Mice Independently of Obesity

The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease

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