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Personal model-assi...
Personal model-assisted identification of NAD(+) and glutathione metabolism as intervention target in NAFLD
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- Mardinoglu, Adil, 1982 (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Björnson, Elias, 1988 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Chalmers tekniska högskola,Chalmers University of Technology
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- Zhang, C. (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Klevstig, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital
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- Soderlund, S. (author)
- Helsinki University Central Hospital
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- Ståhlman, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital
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- Adiels, Martin, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital
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- Hakkarainen, A. (author)
- Helsinki University Central Hospital
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- Lundbom, N. (author)
- Helsinki University Central Hospital
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- Kilicarslan, M. (author)
- Universiteit Van Amsterdam,University of Amsterdam
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- Hallstrom, B. M. (author)
- Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Lundbom, J. (author)
- Helsinki University Central Hospital
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- Verges, B. (author)
- Centre Hospitalier Universitaire de Dijon
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- Barrett, P. H. R. (author)
- University of Western Australia
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- Watts, G. F. (author)
- University of Western Australia
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- Serlie, M. J. (author)
- Universiteit Van Amsterdam,University of Amsterdam
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- Nielsen, Jens B, 1962 (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Uhlén, Mathias (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Smith, Ulf, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital
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- Marschall, Hanns-Ulrich, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Taskinen, M. R. (author)
- Helsinki University Central Hospital
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital
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(creator_code:org_t)
- 2017-03-02
- 2017
- English.
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In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:3
- Related links:
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Abstract
Subject headings
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- To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale 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(+) 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 de novo GSH synthesis. To assess the effect of GSH and NAD(+) repletion on the development of NAFLD, we added precursors for GSH and NAD(+) biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof-of-concept 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- glutathione
- NAFLD
- personalized genome-scale metabolic modeling
- serine
- fatty liver-disease
- amino-acid-metabolism
- tissue blood-flow
- adipose-tissue
- genome-scale
- insulin-resistance
- hepatocellular-carcinoma
- drug targets
- obesity
- muscle
- Biochemistry & Molecular Biology
- urenberg p
- 1991
- british journal of nutrition
- v65
- p105
- zefsky t
- 1976
- journal of clinical investigation
- v57
- p444
- genome-scale
Publication and Content Type
- ref (subject category)
- art (subject category)
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Mardinoglu, Adil ...
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Björnson, Elias, ...
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Zhang, C.
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Klevstig, Martin ...
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Soderlund, S.
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Ståhlman, Marcus ...
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show more...
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Adiels, Martin, ...
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Hakkarainen, A.
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Lundbom, N.
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Kilicarslan, M.
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Hallstrom, B. M.
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Lundbom, J.
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Verges, B.
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Barrett, P. H. R ...
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Watts, G. F.
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Serlie, M. J.
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Nielsen, Jens B, ...
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Uhlén, Mathias
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Smith, Ulf, 1943
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Marschall, Hanns ...
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Taskinen, M. R.
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Borén, Jan, 1963
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- NATURAL SCIENCES
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MEDICAL AND HEAL ...
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Molecular System ...
- By the university
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University of Gothenburg
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Chalmers University of Technology
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Royal Institute of Technology