[PPAR-gamma receptors, new therapeutic target in metabolic and cardiovascular diseases].
PPARs ("Peroxisome Proliferator-Activated Receptors") belong to a superfamily of nuclear receptors with several isoforms, among which PPAR-alpha mainly located in the liver and PPAR-gamma mainly located in the adipose tissue. These receptors are considered as major pharmacological targets since the discovery of their activation by specific agonists, which lead to various favourable metabolic effects. Improvement of lipid profile by fibrates is explained by the activation of liver PPAR-alpha receptors. However, PPAR-gamma receptors have focused most fundamental and clinical research in recent years after the demonstration of their activation by thiazolidinediones (pioglitazone, rosiglitazone), a new class of antidiabetic agents. Beyond their effects on insulin sensitivity, glitazones exert pleiotropic effects that may result in cardiovascular protection in high risk patients. It has been recently demonstrated that certain angiotensin AT1 receptor blockers (sartans) can also exert a partial agonist activity on PPAR-gamma. Among the molecules of this class, telmisartan appears to exert this effect at the lower concentrations. Thus, PPAR-y, as common pharmacological target, may, at least partially, explain some of the effects observed with both thiazolidinediones and inhibitors of the renin-angiotensin system, in particular the improvement in insulin sensitivity (in particular via an increase in adiponectin levels), the protection against type 2 diabetes, the reduction in arterial blood pressure and the prevention of cardiovascular complications. There is currently a major interest from the pharmaceutical industry in the development of new molecules able to activate both PPAR-alpha and PPAR-gamma.
Scheen
A J
AJ
Université de Liege.
Paquot
N
N
D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004345:Drug Industry; D006801:Humans; D007333:Insulin Resistance; D047495:PPAR gamma / Q000494:pharmacology* / Q000502:physiology*; D045162:Thiazolidinediones / Q000627:therapeutic use*
D047495:PPAR gamma; D045162:Thiazolidinediones