Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms

Wang, Cheng; Ma, Cheng; Gong, Lihong; Dai, Shu-Ho; Li, Yunxia

doi:10.1016/j.ejphar.2021.174604

Cited by 37 publications

(22 citation statements)

References 165 publications

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“…Metabolomics analysis showed that CRS altered the metabolic pro le of CCl 4 -induced HF in mice, where the most signi cantly altered pathways were betaine metabolism. Betaine is an important nutrient that is synthesized through the choline metabolic pathway and is an endogenous metabolite [19] . In recent years, a large amount of literature has reported that betaine has good preventive and therapeutic effects on a variety of liver diseases, in addition to maintaining normal physiological functions [20][21][22][23][24] .…”

Section: Discussionmentioning

confidence: 99%

Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway

Zhang

Liu

Huang

et al. 2023

Preprint

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Hepatic fibrosis (HF) could be developed into liver cirrhosis or even hepatocellular carcinoma. Stress has an important role in the occurrence and development of various considerable diseases. However, the effect of a certain degree stress on HF is still controversial. In our study, stress was simulated with regular chronic restraint stress (CRS) and HF model was induced with CCl4 in mice. We found that CRS was able to attenuate CCl4-induced liver injury and fibrosis in mice. Surprisingly, behavioral analysis showed that the mice in the HF group exhibited depression-like behavior. Further, the metabolomic analysis revealed that 119 metabolites and 20 metabolic pathways were altered in mice liver, especially the betaine metabolism pathway. Combined with the results of ingenuity Pathway Analysis (IPA) analysis, the key proteins INSR, PI3K, AKT, and p-AMPK were identified and verified, and the results showed that CRS could upregulate the protein levels and mRNA expression of INSR, PI3K, AKT, and p-AMPK in liver tissues of HF mice. It suggested that CRS alleviated CCl4-induced liver fibrosis in mice through upregulation of the INSR/PI3K/AKT/AMPK pathway. Proper stress might be a potential therapeutic strategy for the treatment of chronic liver disease, which provided new insights into the treatment of HF.

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Section: Discussionmentioning

confidence: 99%

Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway

Zhang

Liu

Huang

et al. 2023

Preprint

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“…When SAM supplementation is provided, SAM maintains the nucleocytoplasmic shuttling of ATRAP mRNA by regulating HuR methylation and upregulates the expression of ATRAP, thereby reducing the disorder of lipid metabolism and insulin resistance (84). One of the main physiological effects of betaine is to get involved in the methionine cycle in the human liver as a methyl donor (136). In addition, experiments in a mouse model have shown that the detected low methylation status of m6A and increased FTO expression could be corrected by betaine supplementation.…”

Section: Potential Drugs Targeting Rbps In Mafldmentioning

confidence: 99%

RNA-binding proteins in metabolic-associated fatty liver disease (MAFLD): From mechanism to therapy

Liu

Shu-qin

et al. 2023

BST

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“…Supplementation of these methyl-donors can lead to an increase in the hepatic outflow of triglycerides [ 44 ]. For example, betaine is a methyl donor generally existing in food, such as spinach and shrimps, that plays an important role in the prevention and therapy of liver diseases including NAFLD [ 45 ]. Interestingly, the DNA methylation pattern of PPARα can be modified by betaine resulting in improved triglyceride content [ 44 , 46 , 47 ].…”

Section: Epigenetic Regulation Of Pparα In Nafldmentioning

confidence: 99%

PPARα in the Epigenetic Driver Seat of NAFLD: New Therapeutic Opportunities for Epigenetic Drugs?

et al. 2022

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Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic and the most common cause of chronic liver disease worldwide. It consists of a spectrum of liver disorders ranging from simple steatosis to NASH which predisposes patients to further fibrosis, cirrhosis and even hepatocarcinoma. Despite much research, an approved treatment is still lacking. Finding new therapeutic targets has therefore been a main priority. Known as a main regulator of the lipid metabolism and highly expressed in the liver, the nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) has been identified as an attractive therapeutic target. Since its expression is silenced by DNA hypermethylation in NAFLD patients, many research strategies have aimed to restore the expression of PPARα and its target genes involved in lipid metabolism. Although previously tested PPARα agonists did not ameliorate the disease, current research has shown that PPARα also interacts and regulates epigenetic DNMT1, JMJD3, TET and SIRT1 enzymes. Moreover, there is a growing body of evidence suggesting the orchestrating role of epigenetics in the development and progression of NAFLD. Therefore, current therapeutic strategies are shifting more towards epigenetic drugs. This review provides a concise overview of the epigenetic regulation of NAFLD with a focus on PPARα regulation and highlights recently identified epigenetic interaction partners of PPARα.

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Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms

Cited by 37 publications

References 165 publications

Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway

Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway

RNA-binding proteins in metabolic-associated fatty liver disease (MAFLD): From mechanism to therapy

PPARα in the Epigenetic Driver Seat of NAFLD: New Therapeutic Opportunities for Epigenetic Drugs?

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