title: Peroxisome proliferator-activated receptor beta/delta as a therapeutic target for metabolic diseases.
abstract: The peroxisome proliferator-activated receptor (PPAR) family comprises three distinct isotypes: PPARalpha, PPARbeta/delta and PPARgamma. PPARs are nuclear hormone receptors that mediate the effects of fatty acids and their derivatives at the transcriptional level. Until recently, the characterisation of the important role of PPARalpha in fatty acid oxidation and of PPARgamma in lipid storage contrasted with the sparse information concerning PPARbeta/delta. However, evidence is now emerging for a role of PPARbeta/delta in tissue repair and energy homeostasis. Experiments with tissue-specific overexpression of PPARbeta/delta or treatment of mice with selective PPARbeta/delta agonists demonstrated that activation of PPARbeta/delta in vivo increases lipid catabolism in skeletal muscle, heart and adipose tissue and improves the serum lipid profile and insulin sensitivity in several animal models. PPARbeta/delta activation also prevents the development of obesity and improves cholesterol homeostasis in obesity-prone mouse models. These new insights into PPARbeta/delta functions suggest that targeting PPARbeta/delta may be helpful for treating disorders associated with the metabolic syndrome. Although these perspectives are promising, several independent and contradictory reports raise concerns about the safety of PPARbeta/delta ligands with respect to tumourigenic activity in the gut. Thus, it appears that further exploration of PPARbeta/delta functions is necessary to better define its potential as a therapeutic target.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bedu
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desvergne
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism*; D047494:PPAR delta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: D047494:PPAR delta; D048068:PPAR-beta