{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:23:31Z","timestamp":1791195811938,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T00:00:00Z","timestamp":1567641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>We recently showed that the functional capacity for ureagenesis is deficient in non\u2010alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to assess expression of urea cycle\u2010related genes to elucidate a possible gene regulatory basis to the functional problem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver mRNA expression analyses within the gene pathway governing hepatic nitrogen conversion were performed in 20 non\u2010diabetic, biopsy\u2010proven NAFLD patients (8 simple steatosis; 12 non\u2010alcoholic steatohepatitis [NASH]) and 12 obese and 14 lean healthy individuals. Sixteen NAFLD patients were included for gene expression validation. Relationship between gene expressions and functional capacity for ureagenesis was described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene expression of most urea cycle\u2010related enzymes were downregulated in NAFLD vs both control groups; markedly so for the urea cycle flux\u2010generating carbamoyl phosphate synthetase (CPS1) (~3.5\u2010fold, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001). In NASH, CPS1 downregulation paralleled the deficit in ureagenesis (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.03). Additionally, expression of several genes involved in amino acid uptake and degradation, and the glucagon receptor gene, were downregulated in NAFLD. Conversely, glutamine synthetase (GS) expression increased &gt;1.5\u2010fold (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a0.03), inversely related to CPS1 expression (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NAFLD downregulated the expression of urea cycle\u2010related genes. Downregulation of urea cycle flux\u2010generating CPS1 correlated with the loss of functional capacity for ureagenesis in NASH. On gene level, these changes coincided with an increase in the major ammonia scavenging enzyme GS. The effects seemed related to a fatty liver as such rather than NASH or obesity. The findings support gene regulatory mechanisms involved in the deficient ureagenesis of NAFLD, but it remains unexplained how hepatocyte fat accumulation exerts these effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14205","type":"journal-article","created":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T13:09:45Z","timestamp":1565096985000},"page":"2094-2101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Non\u2010alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-8308","authenticated-orcid":false,"given":"Peter Lykke","family":"Eriksen","sequence":"first","affiliation":[{"name":"Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus 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