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Abstract: TH-PO782

Ezetimibe Restores the Communication Between Lipid Droplets and Mitochondria via Modulation of Plin5

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology


  • Kim, Jin Ju, University of Miami School of Medicine, Miami, Florida, United States
  • Molina David, Judith T., University of Miami School of Medicine, Miami, Florida, United States
  • Njeim, Rachel, University of Miami School of Medicine, Miami, Florida, United States
  • Miner, Jeffrey H., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Merscher, Sandra M., University of Miami School of Medicine, Miami, Florida, United States
  • Fornoni, Alessia, University of Miami School of Medicine, Miami, Florida, United States

Podocyte lipid accumulation contributes to glomerular diseases such as diabetic kidney disease (DKD) and Alport Syndrome (AS). These excess lipids, such as cholesterol and fatty acids, are esterified and stored as cholesterol ester and triglyceride in lipid droplets. Excessive FFA catabolism resulting from excessive lipolysis of TG is a major contributor to cell lipotoxicity. Perilipin 5 (PLIN5) is an LD-related protein that plays a critical role in regulating TG lipase activity and the interactions between LD and mitochondria, where it protects mitochondria from excessive exposure to FFA. Here we test the hypothesis that PLIN5 expresses in podocytes and that PLIN5 deficiency in AS causes excessive TG breakdown and the loss of LD-mitochondrial contact, thus contributing to kidney failure.


In vitro, Immortalized AS podocytes and WT podocytes were established and characterized in our laboratory by breeding the Col4a3KO mice (Jackson Laboratory) to H-2kb-tsA58 transgenic mice (Charles River). PLIN5 expression was determined by RT-PCR and western blot analysis in podocytes from Col4a3KO mice when compared to controls. TG lipolysis and FFA quantification were determined and normalized to protein content. LD-Mitochondrial contact was determined by TEM analysis. PLIN5 expression was studied in kidney cortexes, and the effect of Ezetimibe on PLIN5 modulation, on LD-Mitochondrial contact, and on podocyte injury was studied in vitro and in vivo.


We demonstrate that PLIN5 is expressed in podocytes, and the expression of PLIN5 is significantly decreased in AS podocytes compared to WT podocytes (p<0.01). AS podocytes also showed significantly increased rates of TG lipolysis (p<0.05), intracellular free fatty acids (p<0.05), and apoptosis (p<0.01) when compared to WT podocytes. AS podocytes had a reduced number of LD-mitochondrial contacts (p<0.05), implying apoptosis. Moreover, Ezetimibe, which restored LD-Mitochondrial contact in vitro (p<0.05) and improved kidney function in vivo, was found to restore PLIN5 expression in vitro and in vivo (p<0.05).


Our study suggests that podocyte PLIN5 deficiency causes podocyte injury in AS through excessive TG lipolysis and inefficient FA transfer from LD to Mitochondria. Ezetimibe improves LD-mitochondria communication by restoring PLIN5 expression.


  • NIDDK Support