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The British Journal of Diabetes & Vascular Disease
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The clinical significance of PPAR{alpha} and {gamma} agonism

Bart Staels

Department of Atherosclerosis, U545 INSERM, Institut Pasteur de Lille, 1 rue du Pr.Calmette BP 245, Lille Cedex, France 59019, Bart.Staels{at}pasteur-lille.fr

The thiazolidinediones are synthetic ligands for nuclear peroxisome proliferator activated receptors (PPARs). PPAR{gamma} is a transcription factor, which in adipose tissue promotes adipocyte differentiation and also induces apoptosis of terminally differentiated insulin-resistant adipocytes. This promotes the appearance of smaller insulin-sensitive cells. PPAR{gamma} ctivation also stimulates the genes controlling triglyceride lipolysis, fatty acid uptake and storage in adipose tissue. It induces a diversion of fatty acids away from muscle and influences the expression of adipocytokines leading to improved insulin signalling in muscle and liver. It may also regulate genes involved in insulin signalling. These all result in an increase in insulin sensitivity. PPAR{gamma} s also expressed in atherosclerotic lesion foam cells and its activation may exert anti-inflammatory actions and stimulate expression of genes involved in the reverse cholesterol transport pathway. Thiazolidinediones also improve lipoprotein metabolism and this activity is most pronounced for agents that activate PPAR{alpha} such as may be the case for pioglitazone.

Key Words: adipocytes • atherosclerosis • insulin resistance • PPAR receptors • pioglitazone • thiazolidinedione.

The British Journal of Diabetes & Vascular Disease, Vol. 2, No. 1 suppl, S28-S31 (2002)
DOI: 10.1177/14746514020020010701
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?