Excessive fat intake contributes to the progression of metabolic diseases via cellular injury
and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal
dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In
mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged
lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic
acid, autophagic degradation activity progressively stagnated in association with impaired …