{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Luukkonen PK"],"funding":["NCATS NIH HHS","NIBIB NIH HHS","HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","NCI NIH HHS","Novo Nordisk Fonden","Merck"],"pagination":["e2217543120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9942818"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(4)"],"pubmed_abstract":["Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, in which prognosis is determined by liver fibrosis. A common variant in hydroxysteroid 17-beta dehydrogenase 13 (<i>HSD17B13</i>, rs72613567-A) is associated with a reduced risk of fibrosis in NAFLD, but the underlying mechanism(s) remains unclear. We investigated the effects of this variant in the human liver and in <i>Hsd17b13</i> knockdown in mice by using a state-of-the-art metabolomics approach. We demonstrate that protection against liver fibrosis conferred by the <i>HSD17B13</i> rs72613567-A variant in humans and by the <i>Hsd17b13</i> knockdown in mice is associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase. Furthermore, we show that hepatic pyrimidines are "],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Inhibition of <i>HSD17B13</i> protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis."],"pmcid":["PMC9942818"],"funding_grant_id":["R03 DK124743","MISP 59622","R01 DK119968","P30 DK045735","R01 DK113984","UL1 TR001863","NNF19OC0057503","R01 DK129552","R01 CA124414","NNF18OC0054504","R01 DK135645","P30 DK036836","P30 DK034989","T32 EB001026"],"pubmed_authors":["Yki-Jarvinen H","Zhang D","Petersen KF","Shulman GI","Mooring M","Orho-Melander M","Yimlamai D","Gaspar RC","Kahn M","Sammalkorpi H","Sakuma I","Luukkonen PK","Arola J","Nasiri A","Zhang X","Penttila AK","Juuti A","Zhang XM"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of <i>HSD17B13</i> protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis.","description":"Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, in which prognosis is determined by liver fibrosis. A common variant in hydroxysteroid 17-beta dehydrogenase 13 (<i>HSD17B13</i>, rs72613567-A) is associated with a reduced risk of fibrosis in NAFLD, but the underlying mechanism(s) remains unclear. We investigated the effects of this variant in the human liver and in <i>Hsd17b13</i> knockdown in mice by using a state-of-the-art metabolomics approach. We demonstrate that protection against liver fibrosis conferred by the <i>HSD17B13</i> rs72613567-A variant in humans and by the <i>Hsd17b13</i> knockdown in mice is associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase. Furthermore, we show that hepatic pyrimidines are ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-29T07:44:04.542Z","creation":"2025-02-19T01:18:18.184Z"},"accession":"S-EPMC9942818","cross_references":{"pubmed":["36669104"],"doi":["10.1073/pnas.2217543120"]}}