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Sökning: onr:"swepub:oai:DiVA.org:oru-80607" > Hydroxysteroid 17-β...

Hydroxysteroid 17-β dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease

Luukkonen, Panu K. (författare)
Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland; Yale School of Medicine, Yale University, New Haven, Connecticut, USA,Helsinki University of Technology
Tukiainen, Taru (författare)
Institute for Molecular Medicine Finland, Helsinki, Finland,Institute for Molecular Medicine Finland (FIMM),Wihuri Research Institute (WRI)
Juuti, Anne (författare)
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Sammalkorpi, Henna (författare)
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Haridas, P. A. Nidhina (författare)
Minerva Foundation Institute for Medical Research, Helsinki, Finland
Niemelä, Onni (författare)
Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and University of Tampere, Tampere, Finland
Arola, Johanna (författare)
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Orho-Melander, Marju (författare)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
Hakkarainen, Antti (författare)
Department 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,Helsinki University Central Hospital
Kovanen, Petri T. (författare)
Wihuri Research Institute, Helsinki, Finland
Dwivedi, Om (författare)
Institute for Molecular Medicine Finland, Helsinki, Finland,Institute for Molecular Medicine Finland (FIMM)
Groop, Leif (författare)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Institute for Molecular Medicine Finland (FIMM)
Hodson, Leanne (författare)
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom
Gastaldelli, Amalia (författare)
Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Pisa, Italy,CNR Institute of Clinical Physiology (IFC-CNR)
Hyötyläinen, Tuulia, 1971- (författare)
Örebro University,Örebro universitet,Institutionen för naturvetenskap och teknik
Oresic, Matej, 1967- (författare)
Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
Yki-Järvinen, Hannele (författare)
Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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 (creator_code:org_t)
2020-03-12
2020
Engelska.
Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:5
Relaterad länk:
https://doi.org/10.1...
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https://doi.org/10.1...
http://dx.doi.org/10...
https://urn.kb.se/re...
https://doi.org/10.1...
https://lup.lub.lu.s...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Carriers of the hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk of NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, and transcriptome using ultra performance liquid chromatography-mass spectrometry and RNA-seq. In carriers and noncarriers of the gene variant, we also measured pathways of hepatic fatty acids (de novo lipogenesis [DNL] and adipose tissue lipolysis [ATL] using 2H2O and 2H-glycerol) and insulin sensitivity using 3H-glucose and euglycemic-hyperinsulinemic clamp) and plasma cytokines. Carriers and noncarriers had similar age, sex and BMI. Fibrosis was significantly less frequent while phospholipids, but not other lipids, were enriched in the liver in carriers compared with noncarriers. Expression of 274 genes was altered in carriers compared with noncarriers, consisting predominantly of downregulated inflammation-related gene sets. Plasma IL-6 concentrations were lower, but DNL, ATL and hepatic insulin sensitivity were similar between the groups. In conclusion, carriers of the HSD17B13 variant have decreased fibrosis and expression of inflammation-related genes but increased phospholipids in the liver. These changes are not secondary to steatosis, DNL, ATL, or hepatic insulin sensitivity. The increase in phospholipids and decrease in fibrosis are opposite to features of choline-deficient models of liver disease and suggest HSD17B13 as an attractive therapeutic target.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Fibrosis
Genetic variation
Hepatitis
Hepatology
Metabolism

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