Are peroxisome proliferator-activated receptors involved in skeletal muscle wasting during experimental cancer cachexia? Role of beta2-adrenergic agonists.
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 beta(2)-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.
Fuster
Gemma
G
Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Busquets
Sílvia
S
Ametller
Elisabet
E
Olivan
Mireia
M
Almendro
Vanessa
V
de Oliveira
Cibely Cristine Fontes
CC
Figueras
Maite
M
López-Soriano
Francisco J
FJ
Argilés
Josep M
JM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D002100:Cachexia; D005227:Fatty Acids / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D050356:Lipid Metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy; D009374:Neoplasms, Experimental; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D000318:Adrenergic beta-Agonists; D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors