UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation

Gallego-Durán, R; Ampuero, J; Pastor-Ramírez, H; Álvarez-Amor, L; del Campo, JA; Maya-Miles, D; Montero-Vallejo, R; ... Romero-Gómez, M; + view all (2022) Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation. Scientific Reports , 12 (1) , Article 3418. 10.1038/s41598-022-06614-9. (In press). Green open access

[thumbnail of Jalan_s41598-022-06614-9.pdf]
Preview
Text
Jalan_s41598-022-06614-9.pdf - Published Version

Download (1MB) | Preview

Abstract

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 werefound 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.

Type: Article
Title: Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-022-06614-9
Publisher version: https://doi.org/10.1038/s41598-022-06614-9
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Gastroenterology, Health care, Medical research
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10145230
Downloads since deposit
31Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item