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

Liver International Aug 14, 2019

Eriksen PL, Vilstrup H, Rigbolt K, et al. - Researchers determined gene expression of urea cycle enzymes and gene expression related to hepatic nitrogen conversion in liver biopsies from non-alcoholic fatty liver disease (NAFLD) patients vs obese and non-NAFLD lean people. In 20 non-diabetic, biopsy-proven NAFLD patients and 12 obese and 14 lean healthy people, liver mRNA expression analyses within the gene pathway governing hepatic nitrogen conversion were performed. For gene expression validation, 16 NAFLD patients were involved. Findings suggested that NAFLD has downregulated gene expression associated with the urea cycle. Downregulation of the flux-generating CPS1 urea cycle associated with the loss of ureagenesis functional ability in non-alcoholic steatohepatitis (NASH). These modifications coincided with a rise in the significant ammonia scavenging enzyme GS at the gene level. The impacts, instead of NASH or obesity, seemed to be linked to a fatty liver as such. The results support gene regulatory processes engaged in NAFLD's deficient ureagenesis, but how the accumulation of hepatocyte fat exerts these effects remains unexplained.
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