Methionine cycle in nonalcoholic fatty liver disease and its potential applications

Wang, Haoyu; Wu, Yan‐Chao; Tang, Wei

doi:10.1016/j.bcp.2022.115033

Cited by 10 publications

(6 citation statements)

References 172 publications

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“…[62] Methionine can also be converted into antioxidant glutathione. [63] Therefore, these six metabolites mainly promoted lipolysis, fatty acids oxidation, lipids transport, and decreased oxidative stress to alleviate NAFLD in aged hens. They involved metabolic pathways included linoleic acid metabolism, cysteine and methionine metabolism, carnitine metabolism as well as pantothenic acid and CoA biosynthesis metabolism, which were regulated by taurine to increase the levels of the above six metabolites to alleviate NAFLD (Figure 9).…”

Section: Discussionmentioning

confidence: 99%

Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model

Yu,

Cheng,

Luo

et al. 2023

Molecular Nutrition Food Res

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ScopeAged laying hen is recently suggested as a more attractive animal model than rodent for studying nonalcoholic fatty liver disease (NAFLD) of humans. This study aims to reveal effects and metabolic regulation mechanisms of taurine alleviating NAFLD by using the aged laying hen model.Methods and resultsLiver histomorphology and biochemical indices show 0.02% taurine effectively alleviated fat deposition and liver damage. Comparative liver lipidomics and gene expressions analyses reveal taurine promoted lipolysis, fatty acids oxidation, lipids transport, and reduced oxidative stress in liver. Furthermore, comparative serum metabolomics screen six core metabolites negatively correlated with NAFLD, including linoleic acid, gamma‐linolenic acid, pantothenate, L‐methionine, 2‐methylbutyroylcarnitine, L‐carnitine; and two core metabolites positively correlated with NAFLD, including lysophosphatidylcholine (14:0/0:0) and lysophosphatidylcholine (16:0/0:0). Metabolic pathway analysis reveals taurine mainly regulated linoleic acid metabolism, cysteine and methionine metabolism, carnitine metabolism, pantothenic acid and coenzyme A biosynthesis metabolism, and glycerophospholipid metabolism to up‐adjust levels of six negatively correlated metabolites and down‐adjust two positively correlated metabolites for alleviating NAFLD of aged hens.ConclusionThis study firstly reveals underlying metabolic mechanisms of taurine alleviating NAFLD using the aged hen model, thereby laying the foundation for taurine's application in the prevention of NAFLD in both human and poultry.

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Section: Discussionmentioning

confidence: 99%

Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model

Yu,

Cheng,

Luo

et al. 2023

Molecular Nutrition Food Res

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“…MAFLD is a chronic metabolic disease, and its exact pathogenesis is still unclear. At present, precise biomarkers and specific drugs for diagnosing and treating MAFLD still need to be discovered [ 17 ]. In addition, currently, invasive biopsy is the most common method in detecting nonalcoholic steatohepatitis (NAS), so there are still many limitations.…”

Section: Etabolic-associated Fatty Liver Diseasementioning

confidence: 99%

Current insights into the interplay between gut microbiota-derived metabolites and metabolic-associated fatty liver disease

Dongoran,

Tu,

Liu

2023

Tzu Chi Medical Journal

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent and challenging disease associated with a significant health and economic burden. MAFLD has been subjected to and widely investigated in many studies; however, the underlying pathogenesis and its progression have yet to understand fully. Furthermore, precise biomarkers for diagnosing and specific drugs for treatment are yet to be discovered. Increasing evidence has proven gut microbiota as the neglected endocrine organ that regulates homeostasis and immune response. Targeting gut microbiota is an essential strategy for metabolic diseases, including MAFLD. Gut microbiota in the gut-liver axis is connected through tight bidirectional links through the biliary tract, portal vein, and systemic circulation, producing gut microbiota metabolites. This review focuses on the specific correlation between gut microbiota metabolites and MAFLD. Gut microbiota metabolites are biologically active in the host and, through subsequent changes and biological activities, provide implications for MAFLD. Based on the review studies, gut-liver axis related-metabolites including short-chain fatty acids, bile acids (BAs), lipopolysaccharide, choline and its metabolites, indole and its derivates, branched-chain amino acids, and methionine cycle derivates was associated with MAFLD and could be promising MAFLD diagnosis biomarkers, as well as the targets for MAFLD new drug discovery.

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“…In this model, severe steatosis, NASH and fibrosis occurred after 8 weeks of feeding ( Table 1 ). This is due to impaired beta-oxidation and lipoprotein biosynthesis pathways required by the 2 essential nutrients [ 278 ]. However, a huge disadvantage in using MCD-fed models is that they do not exhibit insulin resistance and obesity [ 213 ], a symptom found in patients’ MAFLD.…”

Section: Mafld Preclinical Modelsmentioning

confidence: 99%

“…Coherently, inclusion of trace amounts (~0.1–0.15% (w/w)) of methionine and/or ~0.06% choline in the diets slowed NASH progression but resulted in obesity, insulin resistance and dyslipidemia at 23 weeks [ 279 ]. Recently, Wang et al [ 278 ] proposed the key role of a disordered methionine cycle in driving NAFLD progression during early steatosis stages. This could possibly provide the link that we observe in MCD-aggravated liver disease, independent of metabolic dysregulation [ 278 ].…”

Section: Mafld Preclinical Modelsmentioning

confidence: 99%

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Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm

Chua

Low

Cheam

et al. 2022

IJMS

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Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.

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Methionine cycle in nonalcoholic fatty liver disease and its potential applications

Cited by 10 publications

References 172 publications

Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model

Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model

Current insights into the interplay between gut microbiota-derived metabolites and metabolic-associated fatty liver disease

Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm

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