Increase in muscle mitochondrial biogenesis does not prevent muscle loss but increased tumor size in a mouse model of acute cancer-induced cachexia

Xiao Wang, Alicia M. Pickrell, Teresa Zimmers, Carlos T. Moraes

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cancer-associated cachexia is a complex metabolic condition characterized by the progressive loss of body fat and deterioration of muscle mass. Although the cellular and molecular mechanisms of cachexia are incompletely understood, previous studies have suggested mitochondrial dysfunction in murine models of cancer cachexia. To better understand the metabolic shift in cancer-induced cachexia, we studied the effects of enhanced oxidative capacity on muscle wasting using transgenic mice over-expressing Peroxisome Proliferator-Activated Receptor gamma Co-activator-1α (PGC-1α) in skeletal muscle in a Lewis lung carcinoma-implanted model. Increased mitochondrial biogenesis was observed in the skeletal muscle of tumor-implanted mice. However, these increases did not prevent or reverse muscle wasting in mice harboring tumors. Moreover, tumor size was increased in muscle PGC-1α over-expressing mice. We found similar levels of circulating inflammatory cytokines in tumor-implanted animals, which was not affected by increased muscle expression of PGC-1α. Our data indicated that increased mitochondrial biogenesis in skeletal muscle is not sufficient to rescue tumor-associated, acute muscle loss, and could promote tumor growth, possibly through the release of myokines.

Original languageEnglish (US)
Article numbere33426
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 12 2012
Externally publishedYes

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cachexia
Cachexia
Organelle Biogenesis
Muscle
Tumors
animal models
Muscles
muscles
neoplasms
Neoplasms
skeletal muscle
Skeletal Muscle
mice
Lewis Lung Carcinoma
biogenesis
PPAR gamma
Transgenic Mice
body fat
carcinoma
Deterioration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Increase in muscle mitochondrial biogenesis does not prevent muscle loss but increased tumor size in a mouse model of acute cancer-induced cachexia. / Wang, Xiao; Pickrell, Alicia M.; Zimmers, Teresa; Moraes, Carlos T.

In: PLoS One, Vol. 7, No. 3, e33426, 12.03.2012.

Research output: Contribution to journalArticle

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