Role of Sphingosine Kinases in the Development of NAFLD and HCC

Abstract

Sphingolipids are a class of essential lipids, serving as both building blocks of the cell membrane that facilitate cell growth and proliferation and acting as signalling molecules that dictate various cell functions. The liver stands as the primary site for sphingolipid metabolism in our bodies. Conversely, dysregulation of sphingolipids has been implicated in a broad range of liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic hepatosteatosis (NASH) and hepatocellular carcinoma (HCC). Currently, there are no FDA-approved drugs for NAFLD progression to NASH, while the first-line treatments for HCC exhibit limited effectiveness and high rates of severe adverse reactions. Therefore, pinpointing pathogenic sphingolipids and exploiting sphingolipid-based therapeutic avenues remain pressing concerns in liver research.