Roles of peroxisome proliferator-activated receptor delta (PPARdelta) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome.
Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors playing important regulatory functions in development and metabolism. PPARalpha and PPARgamma are the most extensively examined and characterized, mainly because they are activated by marketed hypolipidemic and insulin sensitizer compounds, such as fibrates and thiazolidinediones. It has been established that the third member of the family, PPARdelta is implicated in developmental regulations, but until recently, its role in metabolism remained unclear. The availability of specific PPARdelta agonists and of appropriate cellular and animal models revealed that PPARdelta plays a crucial role in fatty acid metabolism in several tissues. Treatment of obese animals with PPARdelta agonists results in normalization of metabolic parameters and reduction of adiposity. Activation of the nuclear receptor promotes fatty acid burning in skeletal muscle and adipose tissue by upregulation of fatty acid uptake, beta-oxidation and energy uncoupling. PPARdelta is also involved in the adaptive metabolic responses of skeletal muscle to environmental changes, such as long-term fasting or physical exercise, by controlling the number of oxidative myofibers. These observations strongly suggest that PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption and decreasing obesity.
Luquet
Serge
S
Inserm U636, Centre de Biochimie, UFR Sciences, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice, France.
Lopez-Soriano
Joaquin
J
Holst
Dorte
D
Gaudel
Céline
C
Jehl-Pietri
Chantal
C
Fredenrich
Alexandre
A
Grimaldi
Paul André
PA
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008024:Ligands; D008253:Macaca mulatta; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D013844:Thiazoles / Q000627:therapeutic use
D005227:Fatty Acids; C425931:GW 501516; D008024:Ligands; D047494:PPAR delta; D013844:Thiazoles