PLIN2 Expression and Lipid Droplet Formation Protect Caki-1 Cells from Palmitate-Induced Lipotoxicity

Lipid droplets are regulated by the perilipin 2 (PLIN2) protein, which is considered to protect against lipotoxicity by sequestering excess lipids. This study investigated the role of PLIN2 in preventing palmitate-induced lipotoxicity in renal Caki-1 cells. Caki-1 cells were treated with palmitate and/or oleate for 24-48 hours and characterized by PLIN2 expression, cell viability, and lipid droplet formation. While both palmitate and oleate upregulated PLIN2 protein, more lipid droplet formation was observed in oleate treated cells. Co-treatment of palmitate (300 µM) with oleate (150 µM) preserved spheroid integrity, significantly increased lipid droplet formation, and reduced palmitate-induced cell death. Knockdown of PLIN2 by siRNA led to an exacerbated palmitate-induced cell apoptosis as evidenced by enhanced cleavage of poly-ADP ribose polymerase (PARP) in PLIN2-deficient cells. Moreover, palmitate stimulated CHOP and p62 and was significantly suppressed by PLIN2 downregulation. These results indicate a cytoprotective role for PLIN2 in palmitate-stimulated Caki-1 cells. Therefore, enhancing PLIN2 expression and lipid droplet formation could be a potential therapeutic strategy to mitigate saturated fatty acid-induced damage in renal tubular epithelial cells. This work was supported by National Institute of Health grant number R16GM149499 and the Atlantis Training Program under grant number TL1DK136047 and U54MD007602. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.