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Human PNPLA3-I148M ...
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Luukkonen, Panu K.Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
(author)
Human PNPLA3-I148M variant increases hepatic retention of polyunsaturated fatty acids
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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2019-08-22
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American Society for Clinical Investigation (ASCI),2019
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:oru-75893
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-75893URI
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https://doi.org/10.1172/jci.insight.127902DOI
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https://lup.lub.lu.se/record/da3c538f-7ab9-425c-8376-78a51918ee9dURI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies:Academy of Finland 309263 282192 307415 312491 EU H2020 project Elucidating Pathways of Steatohepatitis (HY EPoS grant) 634413 H2020-JTI-IMI2 EU project 777377-2 EVO foundation Paulo foundation Sigrid Juselius foundation Finnish Medical foundation Alfred Kordelin foundation Liv och Hälsa foundation
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The common patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant I148M predisposes to nonalcoholic liver disease but not its metabolic sequelae. We compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFA) in vivo in humans and in cells harboring different PNPLA3 genotypes. In 148M homozygous individuals, triglycerides (TGs) in very low-density lipoproteins (VLDL) were depleted of PUFAs both under fasting and postprandial conditions compared with 148I homozygotes, and the PUFA/SFA ratio in VLDL-TGs was lower relative to the chylomicron precursor pool. In human PNPLA3-148M and PNPLA3-KO cells, PUFA but not SFA incorporation into TGs was increased at the expense of phosphatidylcholines, and under lipolytic conditions, PUFA-containing diacylglycerols (DAGs) accumulated compared with PNPLA3-148I cells. Polyunsaturated TGs were increased, while phosphatidylcholines (PCs) were decreased in the human liver in 148M homozygous individuals as compared with 148I homozygotes. We conclude that human PNPLA3-I148M is a loss-of-function allele that remodels liver TGs in a polyunsaturated direction by impairing hydrolysis/transacylation of PUFAs from DAGs to feed phosphatidylcholine synthesis.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Nick, AuliMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland
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Hölttä-Vuori, MaaritMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland
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Thiele, ChristophLIMES Institute, Bonn University, Bonn, Germany,University of Bonn
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Isokuortti, ElinaMinerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Lallukka-Brück, SusannaMinerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Zhou, YouMinerva Foundation Institute for Medical Research, Helsinki, Finland; Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
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Hakkarainen, AnttiDepartment of Radiology, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.9Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland,Finnish National Institute for Health and Welfare,Helsinki University Central Hospital,Helsinki University of Technology
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Lundbom, NinaDepartment of Radiology, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland,Helsinki University Central Hospital
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Peltonen, MarkkuDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland,Finnish National Institute for Health and Welfare
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Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor
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Oresic, Matej,1967-Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland(Swepub:oru)moc
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Hyötyläinen, Tuulia,1971-Örebro University,Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)tihn
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Hodson, LeanneOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom
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Ikonen, ElinaMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland
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Yki-Järvinen, HanneleMinerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland,Helsinki University Central Hospital
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Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland
(creator_code:org_t)
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In:JCI Insight: American Society for Clinical Investigation (ASCI)4:162379-3708
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Zhou, You
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