The Role Of Cd36 In Relieving Lipotoxicity Of Skeletal Muscle Cells In High Free Fatty Acid Environment.

Abstract

PURPOSE: Lipotoxicity is closely related to the etiology and complications of type 2 diabetes mellitus (T2DM). Lipotoxicity in muscle cells induces insulin resistance, which is a key factor in the pathogenesis of T2DM. This study investigated the protective effect of Fatty Acid Translocase (FAT/CD36) against palmitic acid (PA)- induced lipoapoptosis. METHODS: Cells at ~40-60% confluence were transfected with siCtrl or siCD36 for overnight using Lipofectamine RNAiMAX. Cells were treated with PA at 200μM for 16 h. The PA-induced viability in C2C12 cells was measured by MTT assay; the PA-induced apoptosis in C2C12 cells was monitored by flow cytometry. The differences in means were analyzed by t test. RESULTS: PA treatment increased apoptosis (7.50% ± 0.21% vs. 10.40% ± 1.25%, p < 0.05) and decreased viability (100% ± 2.40% vs. 97.32% ± 3.60%, p < 0.05) in C2C12 cells in contrast to cells that were treated with PA-free media. After 16 h of PA treatment without CD36 protection, C2C12 cells had a significant increase in apoptosis when treated with siCD36 transfection, in contrast to cells that were negative control siRNA transfected (10.40% ± 1.25% vs. 16.04% ± 1.58%, p < 0.05), indicating that the existence of CD36 may protect high PA-induced lipoapoptosis by increasing cell uptake of FFA. Further statistical analysis confirmed a significant increase in the percentage of apoptotic cells both in early stage and late stage when subjected to CD36 deficiency (7.93% ± 0.57% vs. 10.70% ± 1.55%, p < 0.05; 2.47% ± 0.68% vs. 5.34% ± 0.06%, p < 0.05, respectively). CONCLUSIONS: This study demonstrated a novel function of CD36 in preventing lipotoxicity in skeletal muscle cells when subject to high FFA environment, implicating a promising target for obesity and diabetic therapy.