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Cancer Research 67, 6512-6519, July 1, 2007. doi: 10.1158/0008-5472.CAN-07-0231
© 2007 American Association for Cancer Research

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Epidemiology and Prevention

Are Peroxisome Proliferator-Activated Receptors Involved in Skeletal Muscle Wasting during Experimental Cancer Cachexia? Role of ß2-Adrenergic Agonists

Gemma Fuster, Sílvia Busquets, Elisabet Ametller, Mireia Olivan, Vanessa Almendro, Cibely Cristine Fontes de Oliveira, Maite Figueras, Francisco J. López-Soriano and Josep M. Argilés

Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain

Requests for reprints: Josep M. Argilés, Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain. Phone: 34-934021002; Fax: 34-934021559; E-mail: jargiles{at}ub.edu.

Implantation of the Yoshida AH-130 ascites hepatoma to rats resulted in a decrease in muscle weight 7 days after the inoculation of the tumor. These changes were associated with increases in the mRNA content for both peroxisome proliferator-activated receptor (PPAR) {gamma} and PPAR{delta} in skeletal muscle. The increase in gene expression for these transcription factors was related to increases in the expression of several genes involved in fatty acid transport, activation, and oxidation. Tumor burden also resulted in increases in PPAR{gamma} coactivator-1{alpha} gene expression and pyruvate dehydrogenase kinase 4. All these changes in lipid metabolism genes suggest that a metabolic shift occurs in skeletal muscle of tumor-bearing rats toward a more oxidative phenotype. Formoterol treatment to tumor-bearing rats resulted in an amelioration of all the changes observed as a result of tumor burden. Administration of this ß2-adrenergic agonist also resulted in a decrease in mRNA content of muscle PPAR{alpha}, PPAR{delta}, and PPAR{gamma}, as well as in mRNA levels of many of the genes involved in both lipid and mitochondrial metabolism. All these results suggest an involvement of the different PPARs as transcription factors related with muscle wasting and also indicate that a possible mode of action of the anticachectic compound formoterol may involve a normalization of the levels of these transcription factors. [Cancer Res 2007;67(13):6512–9]




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G. S. Lynch and J. G. Ryall
Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease
Physiol Rev, April 1, 2008; 88(2): 729 - 767.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.