{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:15:50Z","timestamp":1792617350194,"version":"4.5.0"},"reference-count":152,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 \u03b2-synthase (CBS) and cystathionine \u03b3-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.<\/jats:p>","DOI":"10.3390\/jcm10051081","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:03:15Z","timestamp":1614920595000},"page":"1081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-1072","authenticated-orcid":false,"given":"Mikkel Parsberg","family":"Werge","sequence":"first","affiliation":[{"name":"Gastro Unit, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5728-5321","authenticated-orcid":false,"given":"Adrian","family":"McCann","sequence":"additional","affiliation":[{"name":"Bevital AS, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth Douglas","family":"Galsgaard","sequence":"additional","affiliation":[{"name":"Global Drug Discovery, Novo Nordisk A\/S, Novo Nordisk Park, 2760 M\u00e5l\u00f8v, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorte","family":"Holst","sequence":"additional","affiliation":[{"name":"Global Drug Discovery, Novo Nordisk A\/S, Novo Nordisk Park, 2760 M\u00e5l\u00f8v, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5885-4541","authenticated-orcid":false,"given":"Anne","family":"Bugge","sequence":"additional","affiliation":[{"name":"Global Drug Discovery, Novo Nordisk A\/S, Novo Nordisk Park, 2760 M\u00e5l\u00f8v, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-5753","authenticated-orcid":false,"given":"Nicolai J. Wewer","family":"Albrechtsen","sequence":"additional","affiliation":[{"name":"Clinical Proteomic Group, NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-4468","authenticated-orcid":false,"given":"Lise Lotte","family":"Gluud","sequence":"additional","affiliation":[{"name":"Gastro Unit, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/hep.23719","article-title":"Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites","volume":"52","year":"2010","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1053\/j.gastro.2012.02.003","article-title":"Role of Obesity and Lipotoxicity in the Development of Nonalcoholic Steatohepatitis: Pathophysiology and Clinical Implications","volume":"142","author":"Cusi","year":"2012","journal-title":"Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_6","first-page":"3831713","article-title":"Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.freeradbiomed.2016.03.032","article-title":"A Western diet induced NAFLD in LDLR(-\/)(-) mice is associated with reduced hepatic glutathione synthesis","volume":"96","author":"Li","year":"2016","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.metabol.2010.03.006","article-title":"Plasma metabolomic profile in nonalcoholic fatty liver disease","volume":"60","author":"Kalhan","year":"2011","journal-title":"Metabolism"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2169\/internalmedicine.56.7403","article-title":"Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes","volume":"56","author":"Suzuki","year":"2017","journal-title":"Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kabisch, S., B\u00e4ther, S., Dambeck, U., Kemper, M., Gerbracht, C., Honsek, C., Sachno, A., and Pfeiffer, A.F.H. (2018). Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet. Nutrients, 10.","DOI":"10.3390\/nu10020157"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s00125-016-3910-y","article-title":"EASL\u2013EASD\u2013EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease: Is universal screening appropriate?","volume":"59","author":"Byrne","year":"2016","journal-title":"Diabetologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1136\/gutjnl-2018-317584","article-title":"Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease","volume":"68","author":"Caussy","year":"2019","journal-title":"Gut"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.jhep.2019.03.033","article-title":"Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease","volume":"71","author":"Srivastava","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"G1009","DOI":"10.1152\/ajpgi.00283.2016","article-title":"Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to a potential antifibrotic therapy","volume":"311","author":"Karsdal","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jhep.2010.03.029","article-title":"Impaired homocysteine transsulfuration is an indicator of alcoholic liver disease","volume":"53","author":"Medici","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/cjpp-2014-0394","article-title":"The CBS\/CSE system: A potential therapeutic target in NAFLD?","volume":"93","author":"Sarna","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.phrs.2016.07.040","article-title":"Targeting the transsulfuration-H2S pathway by FXR and GPBAR1 ligands in the treatment of portal hypertension","volume":"111","author":"Fiorucci","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1007\/s00018-006-6249-6","article-title":"Betaine homocysteine S-methyltransferase: Just a regulator of homocysteine metabolism?","volume":"63","author":"Pajares","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0955-2863(90)90070-2","article-title":"Methionine metabolism in mammals","volume":"1","author":"Finkelstein","year":"1990","journal-title":"J. Nutr. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/ajcn\/85.1.19","article-title":"Methyl balance and transmethylation fluxes in humans","volume":"85","author":"Mudd","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cbpa.2015.10.030","article-title":"Metabolic control of methylation and acetylation","volume":"30","author":"Su","year":"2016","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10545-009-9006-9","article-title":"Dealing with methionine\/homocysteine sulfur: Cysteine metabolism to taurine and inorganic sulfur","volume":"34","author":"Stipanuk","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/bph.14446","article-title":"Regulators of the transsulfuration pathway","volume":"176","author":"Sbodio","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42912","DOI":"10.1074\/jbc.M206588200","article-title":"Hormonal Regulation of Cystathionine \u03b2-Synthase Expression in Liver","volume":"277","author":"Ratnam","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1210\/en.2012-1658","article-title":"Hydrogen Sulfide Impairs Glucose Utilization and Increases Gluconeogenesis in Hepatocytes","volume":"154","author":"Zhang","year":"2013","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"G1266","DOI":"10.1152\/ajpgi.90484.2008","article-title":"H2S contributes to the hepatic arterial buffer response and mediates vasorelaxation of the hepatic artery via activation of KATP channels","volume":"295","author":"Siebert","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/hep.20817","article-title":"The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis","volume":"42","author":"Fiorucci","year":"2005","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6489","DOI":"10.1073\/pnas.0509531103","article-title":"S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity","volume":"103","author":"Prudova","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1089\/ars.2014.5891","article-title":"S-Glutathionylation Enhances Human Cystathionine \u03b2-Synthase Activity Under Oxidative Stress Conditions","volume":"22","author":"Niu","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1515\/CCLM.2007.341","article-title":"Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine","volume":"45","author":"Finkelstein","year":"2007","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1039\/B604182P","article-title":"Properties of an unusual heme cofactor in PLP-dependent cystathionine \u03b2-synthase","volume":"24","author":"Singh","year":"2007","journal-title":"Nat. Prod. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"H114","DOI":"10.1152\/ajpheart.00087.2015","article-title":"Cystathionine \u03b3-lyase, a H2S-generating enzyme, is a GPBAR1-regulated gene and contributes to vasodilation caused by secondary bile acids","volume":"309","author":"Renga","year":"2015","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"ra72","DOI":"10.1126\/scisignal.2000464","article-title":"H2S Signals Through Protein S-Sulfhydration","volume":"2","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/jn\/136.8.2141","article-title":"Vitamin B-6 deficiency suppresses the hepatic transsulfuration pathway but increases glutathione concentration in rats fed AIN-76A or AIN-93G diets","volume":"136","author":"Lima","year":"2006","journal-title":"J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0955-2863(97)89666-0","article-title":"Elevations of serum cystathionine and total homocysteine in pyridoxine-, folate-, and cobalamin-deficient rats","volume":"8","author":"Stabler","year":"1997","journal-title":"J. Nutr. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.biochi.2015.12.020","article-title":"Vitamin B6 nutritional status and cellular availability of pyridoxal 5\u2032-phosphate govern the function of the transsulfuration pathway\u2019s canonical reactions and hydrogen sulfide production via side reactions","volume":"126","author":"Gregory","year":"2016","journal-title":"Biochimie"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1093\/jn\/130.5.1115","article-title":"Vitamin B-6 Deficiency in Rats Reduces Hepatic Serine Hydroxymethyltransferase and Cystathionine \u03b2-Synthase Activities and Rates of In Vivo Protein Turnover, Homocysteine Remethylation and Transsulfuration","volume":"130","author":"Martinez","year":"2000","journal-title":"J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gregory, J.F., Park, Y., Lamers, Y., Bandyopadhyay, N., Chi, Y.-Y., Lee, K., Kim, S., Da Silva, V., Hove, N., and Ranka, S. (2013). Metabolomic Analysis Reveals Extended Metabolic Consequences of Marginal Vitamin B-6 Deficiency in Healthy Human Subjects. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063544"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ejcn.2013.232","article-title":"Vitamin B12: One carbon metabolism, fetal growth and programming for chronic disease","volume":"68","author":"Rush","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lyon, P., Strippoli, V., Fang, B., and Cimmino, L. (2020). B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease. Nutrients, 12.","DOI":"10.3390\/nu12092867"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jimd.12009","article-title":"Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation","volume":"42","author":"Froese","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1093\/jn\/130.8.1894","article-title":"Extremely low activity of methionine synthase in vitamin B-12-deficient rats may be related to effects on coenzyme stabilization rather than to changes in coenzyme induction","volume":"130","author":"Yamada","year":"2000","journal-title":"J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1177\/15648265080292S103","article-title":"Folate and Vitamin B12Metabolism: Overview and Interaction with Riboflavin, Vitamin B6, and Polymorphisms","volume":"29","author":"Shane","year":"2008","journal-title":"Food Nutr. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1073\/pnas.1717877115","article-title":"Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington\u2019s disease","volume":"115","author":"Sbodio","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.3748\/wjg.15.2097","article-title":"Bile-acid-activated farnesoid X receptor regulates hydrogen sulfide production and hepatic microcirculation","volume":"15","author":"Renga","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molcel.2011.10.021","article-title":"Hydrogen Sulfide-Linked Sulfhydration of NF-\u03baB Mediates Its Antiapoptotic Actions","volume":"45","author":"Sen","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1111\/j.1476-5381.2012.01949.x","article-title":"Platelet-derived growth factor-BB induces cystathionine \u03b3-lyase expression in rat mesangial cells via a redox-dependent mechanism","volume":"166","author":"Hassan","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1089\/ars.2012.4944","article-title":"The Gasotransmitter Hydrogen Sulfide Induces Nrf2-Target Genes by Inactivating the Keap1 Ubiquitin Ligase Substrate Adaptor Through Formation of a Disulfide Bond Between Cys-226 and Cys-613","volume":"19","author":"Hourihan","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.redox.2013.08.006","article-title":"Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells","volume":"1","author":"Steele","year":"2013","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.freeradbiomed.2008.10.040","article-title":"Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress","volume":"46","author":"Harvey","year":"2009","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1038\/s41598-017-03776-9","article-title":"H2S and homocysteine control a novel feedback regulation of cystathionine beta synthase and cystathionine gamma lyase in cardiomyocytes","volume":"7","author":"Nandi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/aps.2014.116","article-title":"Farnesoid X receptor: A master regulator of hepatic triglyceride and glucose homeostasis","volume":"36","author":"Jiao","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000282091","article-title":"Bile Acids as Regulators of Hepatic Lipid and Glucose Metabolism","volume":"28","author":"Trauner","year":"2010","journal-title":"Dig. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrgastro.2010.213","article-title":"NF-\u03baB in the liver\u2014linking injury, fibrosis and hepatocellular carcinoma","volume":"8","author":"Luedde","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13098","DOI":"10.1096\/fj.201901304R","article-title":"Hydrogen sulfide signaling in mitochondria and disease","volume":"33","author":"Murphy","year":"2019","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/ars.2008.2282","article-title":"Hydrogen Sulfide Increases Glutathione Production and Suppresses Oxidative Stress in Mitochondria","volume":"12","author":"Kimura","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3389\/fphar.2017.00608","article-title":"H2S-Induced Sulfhydration: Biological Function and Detection Methodology","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Huang, C.W., and Moore, P.K. (2015). H2S synthesizing enzymes: Biochemistry and molecular aspects. Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide, Springer International Publishing. Handbook of Experimental Pharmacology.","DOI":"10.1007\/978-3-319-18144-8_1"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16418","DOI":"10.1074\/jbc.C116.742213","article-title":"Heme-dependent Metabolite Switching Regulates H2S Synthesis in Response to Endoplasmic Reticulum (ER) Stress","volume":"291","author":"Kabil","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cbpa.2017.02.021","article-title":"Catalytic promiscuity and heme-dependent redox regulation of H2S synthesis","volume":"37","author":"Banerjee","year":"2017","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1136\/gutjnl-2017-313778","article-title":"Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase\/hydrogen sulfide pathway","volume":"67","author":"Li","year":"2017","journal-title":"Gut"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/bs.acc.2018.07.004","article-title":"Glutathione as a Marker for Human Disease","volume":"87","author":"Teskey","year":"2018","journal-title":"Adv. Clin. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13005","DOI":"10.1021\/bi001088w","article-title":"The Quantitatively Important Relationship between Homocysteine Metabolism and Glutathione Synthesis by the Transsulfuration Pathway and Its Regulation by Redox Changes\u2020","volume":"39","author":"Mosharov","year":"2000","journal-title":"Biochemistry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1179\/135100003125001260","article-title":"Redox regulation of homocysteine-dependent glutathione synthesis","volume":"8","author":"Vitvitsky","year":"2003","journal-title":"Redox Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"225","DOI":"10.4062\/biomolther.2017.251","article-title":"Effects and Mechanisms of Taurine as a Therapeutic Agent","volume":"26","author":"Schaffer","year":"2018","journal-title":"Biomol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1476-511X-7-38","article-title":"Taurine reduces the secretion of apolipoprotein B100 and lipids in HepG2 cells","volume":"7","author":"Yanagita","year":"2008","journal-title":"Lipids Health Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E439","DOI":"10.1152\/ajpendo.00336.2003","article-title":"The ubiquitin-proteasome system is responsible for cysteine-responsive regulation of cysteine dioxygenase concentration in liver","volume":"286","author":"Stipanuk","year":"2004","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00726-014-1700-8","article-title":"Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate","volume":"46","author":"Jurkowska","year":"2014","journal-title":"Amino Acids"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/nyas.13021","article-title":"Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice","volume":"1363","author":"Niewiadomski","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E668","DOI":"10.1152\/ajpendo.00151.2011","article-title":"Knockout of the murine cysteine dioxygenase gene results in severe impairment in ability to synthesize taurine and an increased catabolism of cysteine to hydrogen sulfide","volume":"301","author":"Ueki","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1053\/j.gastro.2005.02.034","article-title":"Cystathionine \u03b2 Synthase Deficiency Promotes Oxidative Stress, Fibrosis, and Steatosis in Mice Liver","volume":"128","author":"Robert","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1073\/pnas.92.5.1585","article-title":"Mice deficient in cystathionine beta-synthase: Animal models for mild and severe homocyst(e)inemia","volume":"92","author":"Watanabe","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1007\/s11434-014-0722-7","article-title":"Deficiency of cystathionine gamma-lyase and hepatic cholesterol accumulation during mouse fatty liver development","volume":"60","author":"Mani","year":"2015","journal-title":"Sci. Bull."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1365-2362.2008.01963.x","article-title":"Severe liver steatosis correlates with nitrosative and oxidative stress in rats","volume":"38","author":"Grattagliano","year":"2008","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7603","DOI":"10.1074\/jbc.M111.304576","article-title":"Integrated Stress Response Modulates Cellular Redox State via Induction of Cystathionine \u03b3-Lyase","volume":"287","author":"Dickhout","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1152\/physiolgenomics.90339.2008","article-title":"Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver","volume":"37","author":"Navarro","year":"2009","journal-title":"Physiol. Genom."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jhep.2006.07.028","article-title":"Hyperhomocysteinemia due to cystathionine beta synthase deficiency induces dysregulation of genes involved in hepatic lipid homeostasis in mice","volume":"46","author":"Hamelet","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e13630","DOI":"10.14814\/phy2.13630","article-title":"Specific downregulation of cystathionine \u03b2-synthase expression in the kidney during obesity","volume":"6","author":"Liu","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1139\/cjpp-2013-0106","article-title":"High-fat diet stimulates hepatic cystathionine \u03b2-synthase and cystathionine \u03b3-lyase expression","volume":"91","author":"Hwang","year":"2013","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.niox.2014.03.002","article-title":"Effect of feeding a high fat diet on hydrogen sulfide (H2S) metabolism in the mouse","volume":"41","author":"Peh","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1476-511X-10-60","article-title":"High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway","volume":"10","author":"Bravo","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1172\/JCI11596","article-title":"Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways","volume":"107","author":"Werstuck","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1002\/lt.21810","article-title":"Role of hydrogen sulfide in hepatic ischemia-reperfusion-induced injury in rats","volume":"15","author":"Kang","year":"2009","journal-title":"Liver Transplant."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Tan, G., Pan, S., Li, J., Dong, X., Kang, K., Zhao, M., Jiang, X., Kanwar, J.R., Qiao, H., and Jiang, H. (2011). Hydrogen Sulfide Attenuates Carbon Tetrachloride-Induced Hepatotoxicity, Liver Cirrhosis and Portal Hypertension in Rats. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025943"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/jgh.12389","article-title":"Effects of treatment with hydrogen sulfide on methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats","volume":"29","author":"Luo","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13618-014-0022-y","article-title":"Exogenous hydrogen sulfide mitigates the fatty liver in obese mice through improving lipid metabolism and antioxidant potential","volume":"5","author":"Wu","year":"2015","journal-title":"Med. Gas Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"935251","DOI":"10.1155\/2014\/935251","article-title":"Hydrogen Sulfide Ameliorates Ischemia\/Reperfusion-Induced Hepatitis by Inhibiting Apoptosis and Autophagy Pathways","volume":"2014","author":"Cheng","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12072-010-9202-6","article-title":"Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease","volume":"4","author":"Yang","year":"2010","journal-title":"Hepatol. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: Interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.1093\/emboj\/20.21.6008","article-title":"The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener","volume":"20","author":"Zhao","year":"2001","journal-title":"EMBO J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00726-012-1381-0","article-title":"Taurine and liver diseases: A focus on the heterogeneous protective properties of taurine","volume":"46","author":"Miyazaki","year":"2014","journal-title":"Amino Acids"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s00726-018-2605-8","article-title":"Taurine attenuates the development of hepatic steatosis through the inhibition of oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in vitro","volume":"50","author":"Murakami","year":"2018","journal-title":"Amino Acids"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1007\/s00726-011-0962-7","article-title":"Mechanism underlying the antioxidant activity of taurine: Prevention of mitochondrial oxidant production","volume":"42","author":"Jong","year":"2011","journal-title":"Amino Acids"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"R1710","DOI":"10.1152\/ajpregu.00677.2010","article-title":"Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease","volume":"301","author":"Gentile","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1096\/fj.05-5016fje","article-title":"Chronic liver disease is triggered by taurine transporter knockout in the mouse","volume":"20","author":"Warskulat","year":"2006","journal-title":"FASEB J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"916","DOI":"10.15252\/msb.20167422","article-title":"Personal model-assisted identification of NAD + and glutathione metabolism as intervention target in NAFLD","volume":"13","author":"Mardinoglu","year":"2017","journal-title":"Mol. Syst. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.tiv.2011.05.011","article-title":"Cellular glutathione in fatty liver in vitro models","volume":"25","author":"Garcia","year":"2011","journal-title":"Toxicol. Vitr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1038\/labinvest.2010.112","article-title":"Attenuated progression of diet-induced steatohepatitis in glutathione-deficient mice","volume":"90","author":"Haque","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-017-0013-x","article-title":"Glutathione disulfide sensitizes hepatocytes to TNF\u03b1-mediated cytotoxicity via IKK-\u03b2 S-glutathionylation: A potential mechanism underlying non-alcoholic fatty liver disease","volume":"50","author":"Dou","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1126\/science.106.2763.589","article-title":"Rate of Disappearance From Plasma of Intravenously Administered Methionine in Patients With Liver Damage","volume":"106","author":"Kinsell","year":"1947","journal-title":"Science"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/0016-5085(81)90489-3","article-title":"Evidence for impairment of transsulfuration pathway in cirrhosis","volume":"81","author":"Horowitz","year":"1981","journal-title":"Gastroenterology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/hep.1840160125","article-title":"Defective methionine metabolism in cirrhosis: Relation to severity of liver disease","volume":"16","author":"Marchesini","year":"1992","journal-title":"Hepatology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3109\/00365529209000096","article-title":"Sulfur Amino Acid Metabolism in Hepatobiliary Disorders","volume":"27","author":"Martensson","year":"1992","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1053\/jhep.2002.36499","article-title":"Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[2 H3 -methyl-1-13 C]methionine","volume":"36","author":"Russmann","year":"2002","journal-title":"Hepatology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1080\/003655200750023255","article-title":"Is the Increase in Serum Cystathionine Levels in Patients with Liver Cirrhosis a Consequence of Impaired Homocysteine Transsulfuration at the Level of ?-Cystathionase?","volume":"35","author":"Look","year":"2000","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Hasegawa, T., Iino, C., Endo, T., Mikami, K., Kimura, M., Sawada, N., Nakaji, S., and Fukuda, S. (2020). Changed Amino Acids in NAFLD and Liver Fibrosis: A Large Cross-Sectional Study without Influence of Insulin Resistance. Nutrients, 12.","DOI":"10.20944\/preprints202005.0127.v1"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ioannou, G.N., Gowda, G.A.N., Djukovic, D., and Raftery, D. (2020). Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach. Metabolites, 10.","DOI":"10.3390\/metabo10040168"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000353139","article-title":"Methylenetetrahydrofolate Reductase Gene Polymorphism and Serum Homocysteine Levels in Nonalcoholic Fatty Liver Disease","volume":"63","author":"Brochado","year":"2013","journal-title":"Ann. Nutr. Metab."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1475-2891-12-37","article-title":"Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)","volume":"12","author":"Muniz","year":"2013","journal-title":"Nutr. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12937-016-0221-6","article-title":"Association between homocysteine and non-alcoholic fatty liver disease in Chinese adults: A cross-sectional study","volume":"15","author":"Dai","year":"2016","journal-title":"Nutr. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1111\/j.1440-1746.2005.03891.x","article-title":"Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease","volume":"20","author":"Gulsen","year":"2005","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Jia, G., Di, F., Wang, Q., Shao, J., Gao, L., Wang, L., Li, Q., and Li, N. (2015). Non-Alcoholic Fatty Liver Disease Is a Risk Factor for the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142808"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/oby.22667","article-title":"Association of Hepatic Global DNA Methylation and Serum One-Carbon Metabolites with Histological Severity in Patients with NAFLD","volume":"28","author":"Lai","year":"2019","journal-title":"Obesity"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.ejim.2014.09.007","article-title":"Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis","volume":"25","author":"Leach","year":"2014","journal-title":"Eur. J. Intern. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"21202","DOI":"10.3390\/ijms151121202","article-title":"Plasma Levels of Homocysteine and Cysteine Increased in Pediatric NAFLD and Strongly Correlated with Severity of Liver Damage","volume":"15","author":"Pastore","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.nut.2004.03.022","article-title":"Serum folate and homocysteine levels in obese females with non-alcoholic fatty liver","volume":"21","author":"Hirsch","year":"2005","journal-title":"Nutrition"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1665-2681(19)31488-7","article-title":"Serum homocysteine levels in patients with nonalcoholic fatty liver disease","volume":"11","author":"Polyzos","year":"2012","journal-title":"Ann. Hepatol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.gendis.2018.07.003","article-title":"The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China","volume":"6","author":"Wang","year":"2019","journal-title":"Genes Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3164\/jcbn.15-54","article-title":"Association of homocysteine level with biopsy-proven non-alcoholic fatty liver disease: A meta-analysis","volume":"58","author":"Dai","year":"2016","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"51","DOI":"10.15403\/jgld-529","article-title":"Association of Serum Homocysteine Levels with Histological Severity of NAFLD","volume":"29","author":"Xu","year":"2020","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1309\/93G5JG1BF44N65BQ","article-title":"Homocysteine: Clinical Significance and Laboratory Measurement","volume":"37","author":"Hortin","year":"2006","journal-title":"Lab. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/ajcn\/88.3.738","article-title":"Homocysteine, cysteine, and body composition in the Hordaland Homocysteine Study: Does cysteine link amino acid and lipid metabolism?","volume":"88","author":"Elshorbagy","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Satyanarayana, A., Balakrishna, N., Pitla, S., Reddy, P.Y., Mudili, S., Lopamudra, P., Suryanarayana, P., Viswanath, K., Ayyagari, R., and Reddy, G.B. (2011). Status of B-Vitamins and Homocysteine in Diabetic Retinopathy: Association with Vitamin-B12 Deficiency and Hyperhomocysteinemia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026747"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Li, T., Chen, Y., Li, J., Yang, X., Zhang, H., Qin, X., Hu, Y., and Mo, Z. (2015). Serum Homocysteine Concentration Is Significantly Associated with Inflammatory\/Immune Factors. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138099"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1124\/dmd.112.046953","article-title":"Human Liver Methionine Cycle: MAT1A and GNMT Gene Resequencing, Functional Genomics, and Hepatic Genotype-Phenotype Correlation","volume":"40","author":"Ji","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/ng0595-111","article-title":"A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase","volume":"10","author":"Frosst","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e205316","DOI":"10.1001\/jamanetworkopen.2020.5316","article-title":"Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden","volume":"3","author":"Saadeh","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Sun, M.-Y., Zhang, L., Shi, S.-L., and Lin, J.-N. (2016). Associations between Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms and Non-Alcoholic Fatty Liver Disease (NAFLD) Risk: A Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154337"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1399-0004.2004.00250.x","article-title":"Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration","volume":"65","author":"Wang","year":"2004","journal-title":"Clin. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0168-8278(00)80122-1","article-title":"Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma","volume":"33","author":"Avila","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1161\/hy1101.099499","article-title":"Hyperhomocysteinemia in liver cirrhosis: Mechanisms and role in vascular and hepatic fibrosis","volume":"38","author":"Berasain","year":"2001","journal-title":"Hypertension"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1053\/j.gastro.2013.07.047","article-title":"Relationship Between Methylome and Transcriptome in Patients With Nonalcoholic Fatty Liver Disease","volume":"145","author":"Murphy","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3748\/wjg.v20.i4.1079","article-title":"Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease","volume":"20","author":"Wang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1089\/ars.2009.2956","article-title":"Low Levels of Hydrogen Sulfide in the Blood of Diabetes Patients and Streptozotocin-Treated Rats Causes Vascular Inflammation?","volume":"12","author":"Jain","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1007\/s00125-010-1761-5","article-title":"Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide","volume":"53","author":"Whiteman","year":"2010","journal-title":"Diabetologia"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/hep.29465","article-title":"Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance","volume":"67","author":"Gaggini","year":"2018","journal-title":"Hepatology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1021\/pr200629p","article-title":"A comprehensive untargeted metabonomic analysis of human steatotic liver tissue by RP and HILIC chromatography coupled to mass spectrometry reveals important metabolic alterations","volume":"10","author":"Donato","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Lutchmansingh, F.K., Hsu, J.W., Bennett, F.I., Badaloo, A.V., McFarlane-Anderson, N., Gordon-Strachan, G.M., Wright-Pascoe, R.A., Jahoor, F., and Boyne, M.S. (2018). Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198626"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Honda, Y., Kessoku, T., Sumida, Y., Kobayashi, T., Kato, T., Ogawa, Y., Tomeno, W., Imajo, K., Fujita, K., and Yoneda, M. (2017). Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: An open-label, single-arm, multicenter, pilot study. BMC Gastroenterol., 17.","DOI":"10.1186\/s12876-017-0652-3"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jchromb.2016.02.015","article-title":"Pitfalls in the analysis of the physiological antioxidant glutathione (GSH) and its disulfide (GSSG) in biological samples: An elephant in the room","volume":"1019","author":"Giustarini","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1021\/pr200047c","article-title":"A Proton Nuclear Magnetic Resonance Metabonomics Approach for Biomarker Discovery in Nonalcoholic Fatty Liver Disease","volume":"10","author":"Li","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.taap.2013.01.022","article-title":"Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease","volume":"268","author":"Lake","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/oby.21855","article-title":"Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model","volume":"25","author":"Han","year":"2017","journal-title":"Obesity"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00394-011-0294-0","article-title":"Plasma homocysteine level and hepatic sulfur amino acid metabolism in mice fed a high-fat diet","volume":"52","author":"Yun","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3350\/cmh.2017.0019","article-title":"Protein and vitamin B6 intake are associated with liver steatosis assessed by transient elastography, especially in obese individuals","volume":"23","author":"Ferro","year":"2017","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1748065","DOI":"10.1155\/2016\/1748065","article-title":"Vitamin B6 Prevents Endothelial Dysfunction, Insulin Resistance, and Hepatic Lipid Accumulation in Apoe -\/- Mice Fed with High-Fat Diet","volume":"2016","author":"Liu","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3177\/jnsv.59.73","article-title":"High incidence of lipid deposition in the liver of rats fed a diet supplemented with branched-chain amino acids under vitamin B6 deficiency","volume":"59","author":"Kaimoto","year":"2013","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jnutbio.2014.10.014","article-title":"Oral exposure to the anti-pyridoxine compound 1-amino d-proline further perturbs homocysteine metabolism through the transsulfuration pathway in moderately vitamin B6 deficient rats","volume":"26","author":"Mayengbam","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Mascolo, E., and Vern\u00ec, F. (2020). Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103669"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/5\/1081\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:23Z","timestamp":1760160803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/5\/1081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":152,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["jcm10051081"],"URL":"https:\/\/doi.org\/10.3390\/jcm10051081","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}