2026-08-05T11:42:05Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/187702024-09-21T18:51:35Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16958col_20.500.12105_16980

00925njm 22002777a 4500 dc Gallego-Durán, Rocío author Ampuero, Javier author Pastor-Ramírez, Helena author Álvarez-Amor, Leticia author Del Campo, Jose Antonio author Maya-Miles, Douglas author Montero-Vallejo, Rocío author Cárdenas-García, Antonio author Pareja, Mª Jesús author Gato-Zambrano, Sheila author Millán, Raquel author Del Carmen Rico, María author Luque-Sierra, Amparo author Gil-Gómez, Antonio author Rojas, Ángela author Muñoz-Hernández, Rocío author García-Lozano, María author Aller, Rocío author Andrade, Raúl J author García-Monzón, Carmelo author Andreola, Fausto author Martín, Francisco author Jalan, Rajiv author Romero-Gómez, Manuel author 2022-03-01 The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr -/-). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m2), diabetes mellitus and ALT were found to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears. 10.1038/s41598-022-06614-9 2045-2322 Scientific reports http://hdl.handle.net/10668/19588 35232986 http://hdl.handle.net/20.500.12105/18770 Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation.