Association between Lysosomal Dysfunction and Obesity-Related Pathology: A Key Knowledge to Prevent Metabolic Syndrome

Obesity causes various health problems, such as type 2 diabetes, non-alcoholic fatty liver disease, and cardio- and cerebrovascular diseases. Metabolic organs, particularly white adipose tissue (WAT) and liver, are deeply involved in obesity. WAT contains many adipocytes with energy storage capacity and secretes adipokines depending on the obesity state, while liver plays pivotal roles in glucose and lipid metabolism. This review outlines and underscores the relationship between obesity and lysosomal functions, including lysosome biogenesis, maturation and activity of lysosomal proteases in WAT and liver. It has been revealed that obesity-induced abnormalities of lysosomal proteases contribute to inflammation and cellular senescence in adipocytes. Previous reports have demonstrated obesity-induced ectopic lipid accumulation in liver is associated with abnormality of lysosomal proteases as well as other lysosomal enzymes. These studies demonstrate that lysosomal dysfunction in WAT and liver underlies part of the obesity-related pathology, raising the possibility that strategies to modulate lysosomal function may be effective in preventing or treating the metabolic syndrome.