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PPARdelta is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction

Ravnskjaer, Kim
Boergesen, Michael
Nielsen, Tina
Mandrup, Susanne
Published in Journal of lipid research. 2010, vol. 51, no. 6, p. 1370-1379
Abstract The peroxisome proliferator-activated receptor delta (PPARdelta) is implicated in regulation of mitochondrial processes in a number of tissues, and PPARdelta activation is associated with decreased susceptibility to ectopic lipid deposition and metabolic disease. Here, we show that PPARdelta is the PPAR subtype expressed at the highest level in insulinoma cells and rat pancreatic islets. Furthermore, PPARdelta displays high transcriptional activity and acts in pronounced synergy with retinoid-X-receptor (RXR). Interestingly, unsaturated fatty acids mimic the effects of synthetic PPARdelta agonists. Using short hairpin RNA-mediated knockdown, we demonstrate that the ability of unsaturated fatty acids to stimulate fatty acid metabolism is dependent on PPARdelta. Activation of PPARdelta 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 PPARdelta 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 PPARdelta and RXR may be beneficial in the prevention of beta-cell dysfunction.
Keywords AnimalsCell Line, TumorClone CellsDrug SynergismFatty Acids/*metabolism/*pharmacologyGene Expression Regulation/drug effectsGene Knockdown TechniquesGlucose/metabolismInsulin/secretionInsulin-Secreting Cells/*drug effects/*metabolism/pathology/secretionMaleMitochondria/drug effects/*metabolismOleic Acid/pharmacologyOxidation-ReductionPPAR delta/agonists/deficiency/genetics/*metabolismRNA, Small Interfering/geneticsRatsRats, WistarRetinoid X Receptors/agonists/metabolismTranscription, Genetic/drug effects
PMID: 19965574
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Other version: http://www.jlr.org/content/51/6/1370.full.pdf
Research group Mitochondries et métabolisme énergétique (671)
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RAVNSKJAER, Kim et al. PPARdelta is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction. In: Journal of lipid research, 2010, vol. 51, n° 6, p. 1370-1379. doi: 10.1194/jlr.M001123 https://archive-ouverte.unige.ch/unige:21245

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Deposited on : 2012-05-23

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