Novel Lipophagy Inducers as Potential Therapeutics for Lipid Metabolism Disorders.

ABSTRACT: Dysregulation of lipid homeostasis is associated with a wide range of pathologies encompassing neurological, metabolic, cardiovascular, oncological, and renal disorders. We previously showed that lipid droplet (LD) accumulation in podocytes contributes to the progression of diabetic kidney disease (DKD) and reducing LDs preserves podocyte function and prevents albuminuria. Here, we sought to identify compounds that treat pathological LD accumulation. We developed a phenotypic assay using human podocytes and deployed it to screen a combinatorial library comprising over 45 million unique small molecules. This led to the identification of a compound series that effectively reduces LD accumulation in stressed podocytes. Mechanistic studies revealed that these compounds activate lipophagy, redu

SUBMITTER: Njeim R 

PROVIDER: S-EPMC12614113 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature