Inflammation, dyslipidaemia, diabetes and PPars: pharmacological interest of dual PPARalpha and PPARgamma agonists.
Cardiovascular disease (CVD) remains the leading cause of mortality in developed countries. Several risk factors are associated with CVD, including type 2 diabetes, obesity, insulin resistance, dyslipidaemia and hypertension. Different pharmacological therapies have been developed to control these risk factors. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which belong to the nuclear receptor superfamily that controls lipid and glucose metabolism as well as inflammatory risk factors for CVD. PPARalpha agonists, such as the fibrates, correct dyslipidaemia, thus decreasing CVD risk. PPARgamma agonists, such as the glitazones, increase insulin sensitivity and decrease plasma glucose levels in patients with diabetes. Moreover, both PPARalpha and PPARgamma agonists exert anti-inflammatory activities in liver, adipose and vascular tissues. In this review, we focus on the mode of action of PPARalpha and PPARalpha agonists, illustrating the potential of the newly developed dual PPAR agonists for the treatment of global risk in patients with the metabolic syndrome or type 2 diabetes.
Gervois
P
P
Départment d'Athérosclérose, Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille II, Lille, France.
Fruchart
J C
JC
Staels
B
B
D002318:Cardiovascular Diseases / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D047493:PPAR alpha / Q000819:agonists / Q000627:therapeutic use; D047495:PPAR gamma / Q000819:agonists / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000627:therapeutic use; D012307:Risk Factors; D014157:Transcription Factors / Q000819:agonists
D047493:PPAR alpha; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors