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

Liver International : Official Journal of the International Association for the Study of the Liver
Peter Lykke EriksenKaren Louise Thomsen

Abstract

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. 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. 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...Continue Reading

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Citations

Mar 17, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Katrine D GalsgaardJens J Holst
Nov 10, 2020·Hepatology Communications·Julie Steen PedersenNicolai Jacob Wewer Albrechtsen
Feb 13, 2021·Journal of Clinical Medicine·Kristoffer KjærgaardKaren Louise Thomsen
Feb 20, 2021·Scandinavian Journal of Gastroenterology·Sidsel StøyThomas D Sandahl
Mar 7, 2021·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yasushi Imamura Akio Ido
Sep 17, 2020·Molecular Metabolism·Marie Winther-SørensenNicolai J Wewer Albrechtsen
Dec 19, 2020·Journal of Clinical Medicine·Katrine D Galsgaard
Jun 26, 2021·JHEP Reports : Innovation in Hepatology·Malte Palm SuppliFilip Krag Knop

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