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
Titel: | Hydroxysteroid 17-beta dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease |
Författare: | Luukkonen, Panu K.; Tukiainen, Taru; Juuti, Anne; Sammalkorpi, Henna; Haridas, P. A. Nidhina; Niemelä, Onni; Arola, Johanna; Orho-Melander, Marju; Hakkarainen, Antti; Kovanen, Petri T.; Dwivedi, Om; Groop, Leif; Hodson, Leanne; Gastaldelli, Amalia; Hyötyläinen, Tuulia; Oresic, Matej; Yki-Järvinen, Hannele |
Upphovmannens organisation: | HUS Internal Medicine and Rehabilitation Department of Medicine University of Helsinki Genomics of Sex Differences Institute for Molecular Medicine Finland HUS Abdominal Center II kirurgian klinikka HUSLAB Department of Pathology HUS Medical Imaging Center Department of Diagnostics and Therapeutics Centre of Excellence in Complex Disease Genetics |
Datum: | 2020-03-12 |
Språk: | eng |
Sidantal: | 12 |
Tillhör serie: | JCI INSIGHT |
ISSN: | 2379-3708 |
DOI: | https://doi.org/10.1172/jci.insight.132158 |
Permanenta länken (URI): | http://hdl.handle.net/10138/325971 |
Abstrakt: | 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. |
Subject: |
DE-NOVO LIPOGENESIS
INSULIN-RESISTANCE PHOSPHATIDYLCHOLINE CHOLINE GLUCOSE STEATOHEPATITIS INDIVIDUALS HOMEOSTASIS NUTRIENT PACKAGE 3121 General medicine, internal medicine and other clinical medicine |
Referentgranskad: | Ja |
Licens: | unspecified |
Användningsbegränsning: | openAccess |
Parallelpublicerad version: | publishedVersion |
Finansierad av: | Helsingin yliopisto |
Finansierings ID: |
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Filer | Storlek | Format | Granska |
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132158.1_202003 ... 4c1ab43d105aefdf7b5536.pdf | 1.692Mb | Granska/Öppna |