Are peroxisome proliferator-activated receptors involved in skeletal muscle wasting during experimental cancer cachexia? Role of beta2-adrenergic agonists

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Gemma Fuster
  • Sílvia Busquets
  • Elisabet Ametller
  • Mireia Olivan
  • Vanessa Almendro
  • Cibely Fontes Oliveira
  • Maite Figueras
  • Francisco J López-Soriano
  • Josep M Argilés
Externa organisationer
  • University of Barcelona
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)6512-9
TidskriftCancer Research
Volym67
Utgåva nummer13
StatusPublished - 2007 jul 1
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa