Muscle oxidative capacity during IL-6-dependent cancer cachexia

James P. White, Kristen A. Baltgalvis, Melissa J. Puppa, Shuichi Sato, John W. Baynes, James Carson

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Many diseases are associated with catabolic conditions that induce skeletal muscle wasting. These various catabolic states may have similar and distinct mechanisms for inducing muscle protein loss. Mechanisms related to muscle wasting may also be related to muscle metabolism since glycolytic muscle fibers have greater wasting susceptibility with several diseases. The purpose of this study was to determine the relationship between muscle oxidative capacity and muscle mass loss in red and white hindlimb muscles during cancer cachexia development in the ApcMin/+ mouse. Gastrocnemius and soleus muscles were excised from ApcMin/+ mice at 20 wk of age. The gastrocnemius muscle was partitioned into red and white portions. Body mass (-20%), gastrocnemius muscle mass (-41%), soleus muscle mass (-34%), and epididymal fat pad (-100%) were significantly reduced in severely cachectic mice (n = 8) compared with mildly cachectic mice (n = 6). Circulating IL-6 was fivefold higher in severely cachectic mice. Cachexia significantly reduced the mitochondrial DNA-to-nuclear DNA ratio in both red and white portions of the gastrocnemius. Cytochrome c and cytochrome-c oxidase complex subunit IV (Cox IV) protein were reduced in all three muscles with severe cachexia. Changes in muscle oxidative capacity were not associated with altered myosin heavy chain expression. PGC-1α expression was suppressed by cachexia in the red and white gastrocnemius and soleus muscles. Cachexia reduced Mfn1 and Mfn2 mRNA expression and markers of oxidative stress, while Fis1 mRNA was increased by cachexia in all muscle types. Muscle oxidative capacity, mitochondria dynamics, and markers of oxidative stress are reduced in both oxidative and glycolytic muscle with severe wasting that is associated with increased circulating IL-6 levels.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume300
Issue number2
DOIs
StatePublished - Feb 1 2011

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Cachexia
Interleukin-6
Skeletal Muscle
Muscles
Neoplasms
Electron Transport Complex IV
Oxidative Stress
Muscle Neoplasms
Messenger RNA
Myosin Heavy Chains
Muscle Proteins
Hindlimb
Cytochromes c
Mitochondrial DNA
Adipose Tissue
Mitochondria

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Muscle oxidative capacity during IL-6-dependent cancer cachexia. / White, James P.; Baltgalvis, Kristen A.; Puppa, Melissa J.; Sato, Shuichi; Baynes, John W.; Carson, James.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 300, No. 2, 01.02.2011.

Research output: Contribution to journalArticle

White, James P. ; Baltgalvis, Kristen A. ; Puppa, Melissa J. ; Sato, Shuichi ; Baynes, John W. ; Carson, James. / Muscle oxidative capacity during IL-6-dependent cancer cachexia. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2011 ; Vol. 300, No. 2.
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