Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes.
Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARalpha, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism and inflammatory response in liver and other tissues. PPARgamma plays important roles in regulation of proliferation and differentiation of several cell types, including adipose cells. Its activation by thiazolidinediones results in insulin sensibilization and antidiabetic action. Until recently, the physiological functions of PPARdelta remain elusive. The utilization of specific agonists and of appropriate cellular and animal models revealed that PPARdelta has an important role in metabolic adaptation of several tissues to environmental changes. Treatment of obese animals by specific PPARdelta agonists results in normalization of metabolic parameters and reduction of adiposity. The nuclear receptor appeared to be implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue by controlling the expression of genes involved in fatty acid uptake, beta-oxidation and energy uncoupling. PPARdelta is also implicated in the adaptive metabolic response of skeletal muscle to endurance exercise by controlling the number of oxidative myofibers. Given the results obtained with animal models, PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue.
Luquet
Serge
S
Inserm U636, Centre de Biochimie, UFR Sciences, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice, France.
Gaudel
Celine
C
Holst
Dorte
D
Lopez-Soriano
Joaquin
J
Jehl-Pietri
Chantal
C
Fredenrich
Alexandre
A
Grimaldi
Paul A
PA
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009097:Multienzyme Complexes; D047494:PPAR delta; D063991:Mitochondrial Trifunctional Protein