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

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dc.contributor.author Luukkonen, Panu K.
dc.contributor.author Tukiainen, Taru
dc.contributor.author Juuti, Anne
dc.contributor.author Sammalkorpi, Henna
dc.contributor.author Haridas, P. A. Nidhina
dc.contributor.author Niemelä, Onni
dc.contributor.author Arola, Johanna
dc.contributor.author Orho-Melander, Marju
dc.contributor.author Hakkarainen, Antti
dc.contributor.author Kovanen, Petri T.
dc.contributor.author Dwivedi, Om
dc.contributor.author Groop, Leif
dc.contributor.author Hodson, Leanne
dc.contributor.author Gastaldelli, Amalia
dc.contributor.author Hyötyläinen, Tuulia
dc.contributor.author Oresic, Matej
dc.contributor.author Yki-Järvinen, Hannele
dc.date.accessioned 2021-02-05T09:19:01Z
dc.date.available 2021-02-05T09:19:01Z
dc.date.issued 2020-03-12
dc.identifier.citation Luukkonen , P K , Tukiainen , T , Juuti , A , Sammalkorpi , H , Haridas , P A N , Niemelä , O , Arola , J , Orho-Melander , M , Hakkarainen , A , Kovanen , P T , Dwivedi , O , Groop , L , Hodson , L , Gastaldelli , A , Hyötyläinen , T , Oresic , M & Yki-Järvinen , H 2020 , ' Hydroxysteroid 17-beta dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease ' , JCI INSIGHT , vol. 5 , no. 5 , 132158 . https://doi.org/10.1172/jci.insight.132158
dc.identifier.other PURE: 135020614
dc.identifier.other PURE UUID: 159a4269-3a20-434e-b823-9749ae63c848
dc.identifier.other WOS: 000519997400006
dc.identifier.uri http://hdl.handle.net/10138/325971
dc.description.abstract Carriers of the hydroxysteroid 17-beta 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 [ONLI and adipose tissue lipolysis [ATL] using (H2O)-H-2 and H-2-glycerol) and insulin sensitivity using H-3-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, ONL, 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. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof JCI INSIGHT
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject DE-NOVO LIPOGENESIS
dc.subject INSULIN-RESISTANCE
dc.subject PHOSPHATIDYLCHOLINE
dc.subject CHOLINE
dc.subject GLUCOSE
dc.subject STEATOHEPATITIS
dc.subject INDIVIDUALS
dc.subject HOMEOSTASIS
dc.subject NUTRIENT
dc.subject PACKAGE
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Hydroxysteroid 17-beta dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease en
dc.type Article
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.contributor.organization Department of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization Genomics of Sex Differences
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization II kirurgian klinikka
dc.contributor.organization HUSLAB
dc.contributor.organization Department of Pathology
dc.contributor.organization HUS Medical Imaging Center
dc.contributor.organization Department of Diagnostics and Therapeutics
dc.contributor.organization Centre of Excellence in Complex Disease Genetics
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1172/jci.insight.132158
dc.relation.issn 2379-3708
dc.rights.accesslevel openAccess
dc.type.version publishedVersion
dc.relation.funder Helsingin yliopisto
dc.relation.grantnumber

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