TOTAL PROTEOME COMPARISON OF NASH AND NORMAL MICE USING NANO LC-MS

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that encompasses various conditions from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. It's recognized as one of the primary causes of chronic liver disease worldwide. To investigate this further, we used proteomics to compare liver tissues from mice with NASH caused by a high-fat diet (HFD) to that of healthy controls. We collected liver tissue samples from both groups of mice and used nano liquid chromatography-mass spectrometry (nLC-MS) to analyze protein expression changes that might provide insight into the pathogenesis of NASH. Our study revealed significant modifications in the expression of several proteins related to lipid metabolism, oxidative stress response and endoplasmic reticulum (ER) stress response. We observed that proteins involved in lipid biosynthesis, such as alcohol dehydrogenase (ADH) and glutamate oxaloacetate transaminase (GOT2), were upregulated when compared to controls. Furthermore, we observed alterations to ER and oxidative stress proteins in NASH mice such as endoplasmic reticulum chaperone (HSPA5) and glutamate dehydrogenase 1 (GLUD1). Overall, our findings shed some light on the molecular processes driving NASH and highlight their intricate connection between lipid metabolism, oxidative and ER stress in its pathogenesis.