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Program of the European Union","award":["NIH R01DK123763"],"award-info":[{"award-number":["NIH R01DK123763"]}]},{"name":"LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) consortium funded by the Innovative Medicines Initiative (IMI2) Program of the European Union","award":["777377"],"award-info":[{"award-number":["777377"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program and EFPIA","award":["PID2020-114710RB-I00"],"award-info":[{"award-number":["PID2020-114710RB-I00"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program and EFPIA","award":["U01AA026817"],"award-info":[{"award-number":["U01AA026817"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program and EFPIA","award":["NIH R01DK123763"],"award-info":[{"award-number":["NIH R01DK123763"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program and EFPIA","award":["777377"],"award-info":[{"award-number":["777377"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Livers"],"abstract":"<jats:p>One carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides, amino acids, formylated methionyl-tRNA, polyamines, glutathione, phospholipids, detoxification reactions, maintenance of the redox status and the concentration of NAD, and methylation reactions including epigenetic modifications. That is, 1CM functions as a nutrient sensor and integrator of cellular metabolism. A critical process in 1CM is the synthesis of S-adenosylmethionine (SAMe), the source of essentially all the hundreds of millions of daily methyl transfer reactions in a cell. This versatility of SAMe imposes a tight control in its synthesis and catabolism. Much of our knowledge concerning 1CM has been gained from studies in the production and prevention of nonalcoholic fatty liver disease (NAFLD). Here, we discuss in detail the function of the most important enzymes for their quantitative contribution to maintaining the flux of carbon units through 1CM in the liver and discuss how alterations in their enzymatic activity contribute to the development of NAFLD. Next, we discuss NAFLD subtypes based on serum lipidomic profiles with different risk of cardiovascular disease. Among the latter, we highlight the so-called subtype A for its serum lipidomic profile phenocopying that of mice deficient in SAMe synthesis and because its high frequency (about 50% of the NAFLD patients).<\/jats:p>","DOI":"10.3390\/livers2040020","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T01:43:11Z","timestamp":1665279791000},"page":"243-257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["One Carbon Metabolism and S-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes"],"prefix":"10.3390","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-195X","authenticated-orcid":false,"given":"David","family":"Fern\u00e1ndez-Ramos","sequence":"first","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8452-6939","authenticated-orcid":false,"given":"Fernando","family":"Lopitz-Otsoa","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-4105","authenticated-orcid":false,"given":"Oscar","family":"Millet","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-678X","authenticated-orcid":false,"given":"Cristina","family":"Alonso","sequence":"additional","affiliation":[{"name":"OWL Metabolomics, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-3153","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Mato","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"International Consensus Panel. 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