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The acute effect of...
The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
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- Zhang, C. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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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
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- Arif, Muhammad (author)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Abdellah, Tebani (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Lovric, Alen (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Benfeitas, Rui (author)
- KTH,Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Science for Life Laboratory, SciLifeLab,Systembiologi
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- Ozcan, Mehmet (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Juszczak, Kajetan (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Kim, Woonghee (author)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Kim, Jung Tae (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Bidkhori, Gholamreza (author)
- King's College London
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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
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- Bergh, Per-Olof (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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- Adiels, Martin, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Institute of Medicine, Department of Molecular and Clinical Medicine,Institute of Medicine, School of Public Health and Community Medicine
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- Turkez, Hasan (author)
- Atatürk Üniversitesi,Atatürk University
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- Taskinen, Marja-Riitta (author)
- Helsingin Yliopisto,University of Helsinki
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Bosley, Jim (author)
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- Marschall, Hanns-Ulrich, 1954 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Nielsen, Jens B, 1962 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Uhlén, Mathias (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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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
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- Mardinoglu, Adil (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Centre for Host‐Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
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(creator_code:org_t)
- 2020-04-27
- 2020
- English.
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In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Abstract
Subject headings
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- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (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)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- and l-carnitine
- nicotinamide riboside (NR)
- NAFLD
- N-acetyl-l-cysteine (NAC)
- systems medicine
- l-serine
- NAFLD
- l-serine
- N-acetyl-l-cysteine (NAC)
- nicotinamide riboside (NR)
- and l-carnitine
- systems medicine
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Zhang, C.
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Björnson, Elias, ...
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Arif, Muhammad
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Abdellah, Tebani
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Lovric, Alen
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Benfeitas, Rui
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show more...
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Ozcan, Mehmet
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Juszczak, Kajeta ...
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Kim, Woonghee
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Kim, Jung Tae
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Bidkhori, Gholam ...
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Ståhlman, Marcus ...
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Bergh, Per-Olof
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Adiels, Martin, ...
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Turkez, Hasan
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Taskinen, Marja- ...
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Bosley, Jim
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Marschall, Hanns ...
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Nielsen, Jens B, ...
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Uhlén, Mathias
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Borén, Jan, 1963
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Mardinoglu, Adil
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- Articles in the publication
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Molecular System ...
- By the university
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Chalmers University of Technology
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University of Gothenburg
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Stockholm University
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Royal Institute of Technology
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Karolinska Institutet