Lysosomal Disturbances in Metabolic Disorders

This thesis investigated the effect of lysosomal enzymes in metabolic disorders. Detecting early stages of liver diseases such as alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatohepatitis (MASH) is challenging, whereas diagnostic methods are more advanced and effective for identifying these diseases in their later stages. This thesis showed that lysosomal enzyme cathepsin D could use as an early indicator in ALD. Additionally, it is challenging to diagnose metabolic syndrome in adolescents despite it is well established in adults. This thesis showed that another lysosomal enzyme acid phosphatase has the potential to assist with detecting metabolic syndrome in both adolescences and adults. Moreover, as it is currently challenging for treatment of MASH, this thesis demonstrated that extracellular cathepsin D inhibition has the potential benefits for treatment of MASH. Furthermore, cathepsins play a key role in the transition from NASH to hepatocellular carcinoma (HCC) and can be a therapeutic potential target in HCC. In conclusion, lysosomal enzymes play important roles in metabolic disorders and are promising targets for diagnosis and treatment.