Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function

Thomsen, Karen Louise, Gronbaek, Henning, Glavind, Emilie, Hebbard, Lionel, Jessen, Niels, Clouston, Andrew, George, Jacob and Vilstrup, Hendrik (2014) Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function. American Journal of Physiology - Gastrointestinal and Liver Physiology, 307 3: G295-G301. doi:10.1152/ajpgi.00036.2014


Author Thomsen, Karen Louise
Gronbaek, Henning
Glavind, Emilie
Hebbard, Lionel
Jessen, Niels
Clouston, Andrew
George, Jacob
Vilstrup, Hendrik
Title Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function
Journal name American Journal of Physiology - Gastrointestinal and Liver Physiology   Check publisher's open access policy
ISSN 1522-1547
0193-1857
Publication date 2014-08-01
Year available 2014
Sub-type Article (original research)
DOI 10.1152/ajpgi.00036.2014
Open Access Status
Volume 307
Issue 3
Start page G295
End page G301
Total pages 7
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Collection year 2015
Language eng
Formatted abstract
Nonalcoholic steatohepatitis (NASH) is increasing in prevalence, yet its consequences for liver function are unknown. We studied ureagenesis, an essential metabolic liver function of importance for whole body nitrogen homeostasis, in a rodent model of diet-induced NASH. Rats were fed a high-fat, high-cholesterol diet for 4 and 16 wk, resulting in early and advanced experimental NASH, respectively. We examined the urea cycle enzyme mRNAs in liver tissue, the hepatocyte urea cycle enzyme proteins, and the in vivo capacity of urea-nitrogen synthesis (CUNS). Early NASH decreased all of the urea cycle mRNAs to an average of 60% and the ornithine transcarbamylase protein to 10%, whereas the CUNS remained unchanged. Advanced NASH further decreased the carbamoyl phosphate synthetase protein to 63% and, in addition, decreased the CUNS by 20% [from 5.65 ± 0.23 to 4.58 ± 0.30 μmol × (min × 100 g)-1; P = 0.01]. Early NASH compromised the genes and enzyme proteins involved in ureagenesis, whereas advanced NASH resulted in a functional reduction in the capacity for ureagenesis. The pattern of urea cycle perturbations suggests a prevailing mitochondrial impairment by NASH. The decrease in CUNS has consequences for the ability of the body to adjust to changes in the requirements for nitrogen homeostasis e.g., at stressful events. NASH, thus, in terms of metabolic consequences, is not an innocuous lesion, and the manifestations of the damage seem to be a continuum with increasing disease severity.
Keyword Hepatic amino nitrogen conversion
Metabolism
Nonalcoholic fatty liver disease
Rats
Urea synthesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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