Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Inflammatory bowel disease with primary sclerosing cholangitis: A Danish population-based cohort study 1977-2011

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The Effect of Different Training Intensities on Oxidatively Generated Modifications of Nucleic Acids: A Randomized, Controlled Trial

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  3. The Liver-α-Cell Axis and Type 2 Diabetes

    Research output: Contribution to journalReviewResearchpeer-review

  4. Efficacy of Supervised Pelvic Floor Muscle Training and Biofeedback vs Attention-control Treatment in Adults with Fecal Incontinence

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Evaluation of clinical translatability of the diet-induced obese and biopsy-confirmed gubra amylin mouse model of non-alcoholic steatohepatitis

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

View graph of relations

Background & Aims: We recently showed that the functional capacity for ureagenesis is deficient in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to assess expression of urea cycle-related genes to elucidate a possible gene regulatory basis to the functional problem. Methods: Liver mRNA expression analyses within the gene pathway governing hepatic nitrogen conversion were performed in 20 non-diabetic, biopsy-proven NAFLD patients (8 simple steatosis; 12 non-alcoholic 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. Results: Gene expression of most urea cycle-related enzymes were downregulated in NAFLD vs both control groups; markedly so for the urea cycle flux-generating carbamoyl phosphate synthetase (CPS1) (~3.5-fold, P <.0001). In NASH, CPS1 downregulation paralleled the deficit in ureagenesis (P =.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 >1.5-fold (P ≤.03), inversely related to CPS1 expression (P =.004). Conclusions: NAFLD downregulated the expression of urea cycle-related genes. Downregulation of urea cycle flux-generating 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.

Original languageEnglish
JournalLiver international : official journal of the International Association for the Study of the Liver
Volume39
Issue number11
Pages (from-to)2094-2101
Number of pages8
ISSN1478-3223
DOIs
Publication statusPublished - 1 Nov 2019

Bibliographical note

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

    Research areas

  • amino acids, ammonia, glucagon, glutamine synthetase, non-alcoholic steatohepatitis, urea

ID: 57722816