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The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and approximately 25% of the global population may have NAFLD. NAFLD is associated with obesity and metabolic syndrome, but its pathophysiology is complex and only partly understood. The transsulfuration pathway (TSP) is a metabolic pathway regulating homocysteine and cysteine metabolism and is vital in controlling sulfur balance in the organism. Precise control of this pathway is critical for maintenance of optimal cellular function. The TSP is closely linked to other pathways such as the folate and methionine cycles, hydrogen sulfide (H2S) and glutathione (GSH) production. Impaired activity of the TSP will cause an increase in homocysteine and a decrease in cysteine levels. Homocysteine will also be increased due to impairment of the folate and methionine cycles. The key enzymes of the TSP, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are highly expressed in the liver and deficient CBS and CSE expression causes hepatic steatosis, inflammation, and fibrosis in animal models. A causative link between the TSP and NAFLD has not been established. However, dysfunctions in the TSP and related pathways, in terms of enzyme expression and the plasma levels of the metabolites (e.g., homocysteine, cystathionine, and cysteine), have been reported in NAFLD and liver cirrhosis in both animal models and humans. Further investigation of the TSP in relation to NAFLD may reveal mechanisms involved in the development and progression of NAFLD.

Original languageEnglish
Article number1081
JournalJournal of Clinical Medicine
Volume10
Issue number5
Pages (from-to)1-20
Number of pages20
ISSN2077-0383
DOIs
Publication statusPublished - 5 Mar 2021

    Research areas

  • H2S production, cystathionine beta-synthase/cystathionine gamma-lyase (CBS/CSE) system, glutathione, liver fibrosis, non-alcoholic steatohepatitis, sulfur metabolism, H S pro-duction, Sulfur metabolism, Cystathionine β-synthase/cystathionine γ-lyase (CBS/CSE) system, Liver fibrosis, Non-alcoholic steatohepatitis, Glutathione

ID: 64731164