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We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome\u2010scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD\n                    <jats:sup>+<\/jats:sup>\n                    and glutathione (GSH) in subjects with high HS. Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered\n                    <jats:italic>de novo<\/jats:italic>\n                    GSH synthesis. To assess the effect of GSH and NAD\n                    <jats:sup>+<\/jats:sup>\n                    repletion on the development of NAFLD, we added precursors for GSH and NAD\n                    <jats:sup>+<\/jats:sup>\n                    biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof\u2010of\u2010concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.\n                  <\/jats:p>","DOI":"10.15252\/msb.20167422","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T20:10:42Z","timestamp":1488485442000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":182,"title":["Personal model\u2010assisted identification of NAD+ and\u00a0glutathione metabolism as intervention target in NAFLD"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-6090","authenticated-orcid":false,"given":"Adil","family":"Mardinoglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Bjornson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3721-8586","authenticated-orcid":false,"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Klevstig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanni","family":"S\u00f6derlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"St\u00e5hlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Adiels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hakkarainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Lundbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Kilicarslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn M","family":"Hallstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Lundbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Verg\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Hugh R","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald F","family":"Watts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille J","family":"Serlie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-6003","authenticated-orcid":false,"given":"Jens","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4858-8056","authenticated-orcid":false,"given":"Mathias","family":"Uhl\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns\u2010Ulrich","family":"Marschall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja\u2010Riitta","family":"Taskinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Boren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,2]]},"reference":[{"key":"BFMSB167422_CR1","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1111\/j.1572-0241.2001.04129.x","volume":"96","author":"MF Abdelmalek","year":"2001","unstructured":"Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD (2001) Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. 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