Liver tissue metabolic profiling and pathways of non-alcoholic steatohepatitis in rats

The mechanisms of non-alcoholic steatohepatitis (NASH) in hepatocytes are unknown. Our aim is to study the tissue metabolic profiling and pathways of NASH.

We built rat models for simple steatosis and NASH and analyzed the liver extract using a liquid chromatograph-mass spectrometer. The acquired data were processed by multivariate principal component analysis and partial least squares discriminant analysis (PLS-DA) to obtain metabolic profiling. Orthogonal projections to latent structures DA was used to obtain metabolites capable of distinguishing NASH and steatosis. The total differences in the metabolites between groups were analyzed to determine their metabolic pathways.

Principal component analysis showed that the metabolic profiles of NASH and steatosis are different. The PLS-DA modeling revealed a clear separation between two groups with parameters R² Y and Q² Y all greater than 0.7. The orthogonal projections to latent structures DA model identified 171 metabolites capable of distinguishing NASH from steatosis. The identified metabolites are involved in fatty acid metabolism, tryptophan metabolism, the urea cycle, and the citric acid cycle in hepatocytes.

These metabolic profiles and pathways in rat hepatocytes will offer useful information when studying metabolic disorders in patients with NASH.