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Non‐alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion
- Source :
- Eriksen, P L, Vilstrup, H, Rigbolt, K, Suppli, M P, Sørensen, M, Heebøll, S, Veidal, S S, Knop, F K & Thomsen, K L 2019, ' Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion ', Liver International, vol. 39, no. 11, pp. 2094-2101 . https://doi.org/10.1111/liv.14205
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- 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 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.
- Subjects :
- Male
STIMULATION
UREA CYCLE
ammonia
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Gene expression
Urea
CIRRHOSIS
IN-VIVO
Chemistry
INDUCTION
Fatty liver
glutamine synthetase
Middle Aged
Carbamoyl phosphate synthetase
medicine.anatomical_structure
Liver
030220 oncology & carcinogenesis
Hepatocyte
Urea cycle
Female
030211 gastroenterology & hepatology
non-alcoholic steatohepatitis
Adult
medicine.medical_specialty
Carbamoyl-Phosphate Synthase (Ammonia)
urea
Gene Expression Regulation, Enzymologic
03 medical and health sciences
Downregulation and upregulation
Ammonia
Glutamate-Ammonia Ligase
Internal medicine
medicine
Humans
STEATOSIS
Obesity
Gene
ELIMINATION
amino acids
Hepatology
nutritional and metabolic diseases
medicine.disease
COMPONENT
digestive system diseases
Endocrinology
glucagon
Case-Control Studies
Hepatocytes
AMINO-ACID-TRANSPORT
Steatohepatitis
Transcriptome
RESISTANCE
Subjects
Details
- ISSN :
- 14783231 and 14783223
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Liver International
- Accession number :
- edsair.doi.dedup.....53b6eda02378f2bd02db4dc62ba621a0