Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are the major prevalent liver diseases and growing public health problems worldwide. Because MASLD/MASH is known as a risk for progression to cirrhosis and development of hepatocellular carcinoma, therapeutic approaches and biomarkers that reflect the presence and progression of the disease are needed. In recent years, the usefulness of serum L-FABP levels has been reported for monitoring of hepatocellular damage in various liver diseases including MASLD/MASH in humans. Furthermore, it is reported that hepatic L-FABP is a potential therapeutic target. The purpose of this study was to validate the usefulness of serum L-FABP as a liver damage biomarker in the mouse model of MASLD/MASH and to evaluate the function of L-FABP in the pathogenesis of MASLD/MASH. First, we evaluated the changes in serum L-FABP as a liver damage biomarker using a mouse model of MASLD/MASH fed a choline-deficient, methionine-lowered, amino acid-defined, high-fat diet. The results demonstrated that serum L-FABP levels in the MASLD/MASH model continuously increased with the progression of steatosis and correlated with histopathologic changes. Serum L-FABP may be a useful biomarker for liver disease with respect to translational research bridging between animal models and human clinical research. Further, we showed that in human L-FABP chromosomal transgenic mice L-FABP had a suppressive effect on the gene expression associated with oxidative stress, fibrosis, and inflammation in the MASLD/MASH model. L-FABP is not only a biomarker in the blood but also has the functional aspect of hepatoprotection against MASLD/MASH.