PPARδ Activation Rescues Pancreatic β-Cell Line INS-1E from Palmitate-Induced Endoplasmic Reticulum Stress through Enhanced Fatty Acid Oxidation

One of the key factors responsible for the development of type 2 diabetes is the loss of functional pancreatic β cells. This occurs due to a chronic exposure to a high fatty acid environment. ER stress is caused by an accumulation of irreversible misfold or unfold protein: these trigger the death of functional pancreatic β cells. PPAR δ is an orphan nuclear receptor. It plays a pivotal role in regulating the metabolism of dietary lipids and fats. However, the correlation between PPAR δ of fatty acids and ER stress of pancreatic β cells is not quite clear till date. Here, we show that PPAR δ attenuates palmitate-induced ER stress of pancreatic β cells. On the other hand, PPAR δ agonist inhibits both abnormal changes in ER structure and activation of signaling cascade, which is downstream ER stress. Further, we illustrate that PPAR δ attenuates palmitate-induced ER stress by promoting fatty acid oxidation through treatment with etomoxir, an inhibitor of fatty acid oxidation. It dramatically abolishes PPAR δ -mediated inhibition of ER stress. Finally, we show that PPAR δ could protect pancreatic β cells from palmitate-induced cell death and dysfunction of insulin secretion. Our work elucidates the protective effect of PPAR δ on the fatty-acid-induced toxicity of pancreatic β cells.