出版社：American Society for Biochemistry and Molecular Biology
摘要：The peroxisome proliferator-activated receptor δ (PPARδ) is implicated in regulation of mitochondrial processes in a number of tissues, and PPARδ activation is associated with decreased susceptibility to ectopic lipid deposition and metabolic disease. Here, we show that PPARδ is the PPAR subtype expressed at the highest level in insulinoma cells and rat pancreatic islets. Furthermore, PPARδ displays high transcriptional activity and acts in pronounced synergy with retinoid-X-receptor (RXR). Interestingly, unsaturated fatty acids mimic the effects of synthetic PPARδ agonists. Using short hairpin RNA-mediated knockdown, we demonstrate that the ability of unsaturated fatty acids to stimulate fatty acid metabolism is dependent on PPARδ. Activation of PPARδ increases the fatty acid oxidation capacity in INS-1E β-cells, enhances glucose-stimulated insulin secretion (GSIS) from islets, and protects GSIS against adverse effects of prolonged fatty acid exposure. The presented results indicate that the nuclear receptor PPARδ is a fatty acid sensor that adapts β-cell mitochondrial function to long-term changes in unsaturated fatty acid levels. As maintenance of mitochondrial metabolism is essential to preserve β-cell function, these data indicate that dietary or pharmacological activation of PPARδ and RXR may be beneficial in the prevention of β-cell dysfunction.
