Dysregulation of lipid metabolism in the pseudolobule promotes region-specific autophagy in hepatitis B liver cirrhosis

Chronic hepatitis B (CHB) infection leads to liver cirrhosis (LC), the end stage of liver fibrosis. The precise diagnosis and effective therapy for hepatitis B cirrhosis are still lacking. It is highly necessary to elucidate the metabolic alteration, especially the spatial distribution of metabolites, in LC progression.

Hepatitis B LC induced region-specific autophagy by increasing the expression of LC3B and p62 in the pseudolobule and by dysregulation of unsaturated fatty acids, amino acids, and PC metabolism. The mass spectrometry imaging system provided additional metabolites' spatial information, which can promote biomarker screening technology and support the exploration of novel mechanisms in LC.

In this study, LC-MS/MS together with an airflow-assisted ionization mass spectrometry imaging system was applied to analyze and compare the metabolites' spatial distribution in healthy control (HC) and hepatitis B LC tissue samples. The liver samples were further divided into several subregions in HC and LC groups based on the anatomical characteristics and clinical features.

Both the LC-MS/MS and mass spectrometry imaging results indicated separated metabolite clusters between the HC and LC groups. The differential metabolites were mainly concentrated in lipid-like molecules and amino acids. The phosphatidylcholines (PCs), lysoPCs, several fatty acids, and amino acids reduced expression in the LC group with region specific. Acyl-CoA thioesterase 2 and choline/ethanolamine phosphotransferase 1, which regulate PC and fatty acid metabolism, were significantly decreased in the pseudolobule. Meanwhile, the increased expression of LC3B and p62 in the pseudolobule indicated the upregulation of autophagy. Conclusions: Hepatitis B LC induced region-specific autophagy by increasing the expression of LC3B and p62 in the pseudolobule and by dysregulation of unsaturated fatty acids, amino acids, and PC metabolism. The mass spectrometry imaging system provided additional metabolites' spatial information, which can promote biomarker screening technology and support the exploration of novel mechanisms in LC.