D-Xylose Ameliorates Non-Alcoholic Fatty Liver Disease by Targeting Macrophage-expressed LYZ Gene.

Abstract

This study investigates the therapeutic effects of D-Xylose, a natural sugar, on non-alcoholic fatty liver disease (NAFLD), focusing on the expression of the lysozyme gene (LYZ) in macrophages. Using the single-cell dataset GSE136103 for NAFLD, researchers analyzed macrophage populations and other groups utilizing the Seurat package in R, while a differential analysis was performed on the NAFLD dataset GSE61260 using the limma package. Both in vitro and in vivo models, including cell culture, mouse models, RT-qPCR, Western blot, ELISA, and histopathological analyses, were employed to examine the effect of D-Xylose on lipid accumulation, LYZ expression, blood lipid levels, and inflammatory responses. The study found a significant upregulation of LYZ in free fatty acid (FFA)-treated cells and mouse liver tissues, with a subsequent reduction after D-Xylose intervention. Treatment with D-Xylose and Amlodipine led to a notable decrease in lipid accumulation, as evidenced by reduced triglyceride and cholesterol levels. D-Xylose demonstrated a greater improvement in lipid metabolism than Amlodipine. Additionally, D-Xylose significantly mitigated inflammatory responses, reducing levels of inflammatory markers such as IL1R, IL6, MYS8, TNF, NF-κB, and IL-1. Furthermore, D-Xylose administration significantly reduced liver weight and liver index, with a positive impact on serum liver function and blood lipid levels. The findings suggest that D-Xylose could be a therapeutic intervention for NAFLD by targeting LYZ expression in macrophages, thereby modulating lipid metabolism and inflammatory responses.