PPARδ is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction
PPARδ is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction
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DOI：
10.1194/jlr.m001123
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发表时间：
2010-06-01
影响因子：
6.5
通讯作者：
Mandrup, Susanne
中科院分区：
文献类型：
--
作者：
Ravnskjaer, Kim;Frigerio, Francesca;Mandrup, Susanne
过氧化物酶体增殖体激活受体（PPAR δ）参与许多组织的线粒体过程的调节，PPAR δ的激活与降低异位脂质沉积和代谢疾病的易感性有关。在这里，我们发现PPAR δ是在胰岛素瘤细胞和大鼠胰岛中表达水平最高的PPAR亚型。此外，PPAR δ表现出高转录活性，并与类视黄酸x受体（RXR）显著协同作用。有趣的是，不饱和脂肪酸模拟合成PPAR受体激动剂的作用。通过短发夹rna介导的敲低，我们证明了不饱和脂肪酸刺激脂肪酸代谢的能力依赖于PPAR δ。PPAR δ的激活增加了INS-1E β细胞的脂肪酸氧化能力，增强了胰岛的葡萄糖刺激胰岛素分泌（GSIS），并保护GSIS免受长时间脂肪酸暴露的不良影响。本研究结果表明，核受体PPAR δ是一种脂肪酸传感器，可使β细胞线粒体功能适应不饱和脂肪酸水平的长期变化。由于线粒体代谢的维持对于维持β细胞功能至关重要，这些数据表明，饮食或药物激活PPAR δ和RXR可能有助于预防β细胞功能障碍。——ravnskjaer， K.， F. friigerio， M. Boergesen， T. Nielsen， P. Maechler， S. MandrupPPAR δ是一种脂肪酸传感器，可增强胰岛素分泌细胞的线粒体氧化，防止脂肪酸诱导的功能障碍。[j] .油脂杂志。2010。51: 1370 - 1379。
The peroxisome proliferator-activated receptor delta (PPAR delta) is implicated in regulation of mitochondrial processes in a number of tissues, and PPAR delta activation is associated with decreased susceptibility to ectopic lipid deposition and metabolic disease. Here, we show that PPAR delta is the PPAR subtype expressed at the highest level in insulinoma cells and rat pancreatic islets. Furthermore, PPAR delta displays high transcriptional activity and acts in pronounced synergy with retinoid-X-receptor (RXR). Interestingly, unsaturated fatty acids mimic the effects of synthetic PPAR delta agonists. Using short hairpin RNA-mediated knockdown, we demonstrate that the ability of unsaturated fatty acids to stimulate fatty acid metabolism is dependent on PPAR delta. Activation of PPAR delta increases the fatty acid oxidation capacity in INS-1E beta-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 PPAR delta is a fatty acid sensor that adapts beta-cell mitochondrial function to long-term changes in unsaturated fatty acid levels. As maintenance of mitochondrial metabolism is essential to preserve beta-cell function, these data indicate that dietary or pharmacological activation of PPAR delta and RXR may be beneficial in the prevention of beta-cell dysfunction.-Ravnskjaer, K., F. Frigerio, M. Boergesen, T. Nielsen, P. Maechler, and S. Mandrup. PPAR delta is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction. J. Lipid Res. 2010. 51: 1370-1379.