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Sökning: WFRF:(Hodson Leanne) > Thiele Christoph > Human PNPLA3-I148M ...

  • Luukkonen, Panu K.Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (författare)

Human PNPLA3-I148M variant increases hepatic retention of polyunsaturated fatty acids

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2019-08-22
  • American Society for Clinical Investigation (ASCI),2019
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-75893
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-75893URI
  • https://doi.org/10.1172/jci.insight.127902DOI
  • https://lup.lub.lu.se/record/da3c538f-7ab9-425c-8376-78a51918ee9dURI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 
  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Nick, AuliMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland (författare)
  • Hölttä-Vuori, MaaritMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland (författare)
  • Thiele, ChristophLIMES Institute, Bonn University, Bonn, Germany,University of Bonn (författare)
  • Isokuortti, ElinaMinerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (författare)
  • Lallukka-Brück, SusannaMinerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (författare)
  • 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 (författare)
  • 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,Helsinki University of Technology,Finnish National Institute for Health and Welfare,Helsinki University Central Hospital (författare)
  • Lundbom, NinaDepartment of Radiology, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland,Helsinki University Central Hospital (författare)
  • Peltonen, MarkkuDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland,Finnish National Institute for Health and Welfare (författare)
  • Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor (författare)
  • 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 (författare)
  • Hyötyläinen, Tuulia,1971-Örebro University,Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)tihn (författare)
  • Hodson, LeanneOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom (författare)
  • Ikonen, ElinaMinerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Medicine, Department of Anatomy, University of Helsinki, Helsinki, Finland (författare)
  • 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 (författare)
  • 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)

Sammanhörande titlar

  • Ingår i:JCI Insight: American Society for Clinical Investigation (ASCI)4:162379-3708

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