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First published online on March 23, 2006
Endocrine Reviews, doi:10.1210/er.2005-0012
A more recent version of this article appeared on May 1, 2006
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Roles of skeletal muscle and PPARs in the development and treatment of obesity

Joaquín López-Soriano, Chiara Chiellini, Margherita Maffei, Paul A. Grimaldi, and Josep M. Argilés*

Department of Endocrinology and Metabolism, section of Endocrinology, Ospedale di Cisanello, University of Pisa, Italy; INSERM U-636, Centre de Biochimie, Parc Valrose, Nice, France; Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain

Metabolic disturbances associated with alterations in lipid metabolism, such as obesity, type-2 diabetes and syndrome X are becoming more and more prominent in western societies. In spite of extensive research in such pathologies and their molecular basis, we are still far from completely understanding how these metabolic perturbations are produced and interrelate, and consequently how to treat them efficiently. The discovery that adipose tissue is, in fact, an endocrine tissue able to secrete active molecules related to lipid homeostasis -the adipokines- has dramatically changed our understanding of the molecular events that take place in such diseases. This knowledge has been further improved by the discovery of peroxisome proliferator-activated receptors (PPARs), and their ligands, at present commonly used for the clinical treatment of lipid disturbances. However, a key point remains to be solved, and that is the role of muscle lipid metabolism, notably because of the main role played by this tissue in the development of such pathologies. In addition, a reciprocal regulation between adipose tissue and skeletal muscle has been proposed. New discoveries on the role of PPARdelta in skeletal muscle functions as well as the secretory capabilities of muscle, now considered as an endocrine tissue, have changed the general point of view on lipid homeostasis, opening new and promising doors for the treatment of lipid disorders.




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