Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease

Abstract

The multiple functions of the lysosome, including degradation, nutrient sensing, signaling, and gene regulation, enable the lysosome to regulate lipid metabolism at different levels. In this review, I summarize the recent studies on lysosomal regulation of lipid metabolism and the alterations of the lysosome functions in the livers affected by nonalcoholic fatty liver disease (NAFLD). NAFLD is a highly prevalent lipid metabolic disorder. The progression of NAFLD leads to nonalcoholic steatohepatitis (NASH) and other severe liver diseases, and thus the prevention and treatments of NAFLD progression are critically needed. Targeting the lysosome is a promising strategy. I also discuss the current manipulations of the lysosome functions in the preclinical studies of NAFLD and propose my perspectives on potential future directions.

Keywords: lipid droplet; lipid transport; lipotoxicity; lysosome dynamics; mTOR.