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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\n                    <jats:sup>2<\/jats:sup>\n                    H\n                    <jats:sub>2<\/jats:sub>\n                    O and\n                    <jats:sup>2<\/jats:sup>\n                    H-glycerol) and insulin sensitivity using\n                    <jats:sup>3<\/jats:sup>\n                    H-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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.132158","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T11:01:43Z","timestamp":1583924503000},"source":"Crossref","is-referenced-by-count":96,"title":["Hydroxysteroid 17-\u03b2 dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease"],"prefix":"10.1172","volume":"5","author":[{"given":"Panu K.","family":"Luukkonen","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."},{"name":"Minerva Foundation Institute for Medical Research, Helsinki, Finland."},{"name":"Yale School of Medicine, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5404-8398","authenticated-orcid":true,"given":"Taru","family":"Tukiainen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Juuti","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henna","family":"Sammalkorpi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.A. 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