Inflammatory Cytokine IL6 and Cachectic Muscle Oxidative Capacity Academic Article uri icon

abstract

  • Cancer cachexia is a condition of severe wasting of both skeletal muscle and adipose tissue. Circulating inflammatory cytokine IL6 can regulate the development of cachexia in the ApcMin/+ mouse, a model of colorectal cancer. The purpose of this study was to determine the effects of cancer cachexia and IL6 overexpression on wasting skeletal muscle oxidative capacity. Gastrocnemius (GAST) muscle mitochondrial number, mitochondrial proteins and PGC1 mRNA expression were quantified. ApcMin/+ mice were stratified by cachexia severity. The GAST muscle was sectioned into red (oxidative) and white (glycolytic) portions to determine phenotype specific wasting. IL6 was overexpressed in a subset of ApcMin/+ mice by in vivo electroporation to accelerate wasting. Severely cachectic mice had an 81% reduction in mitochondrial content when compared to mildly cachectic mice. Both oxidative and glycolytic portions of the GAST reduced PGC1 mRNA expression approximately 40% in severely wasting muscle. IL6 overexpression resulted in a 63% decrease in PGC1 protein expression. Cox IV and Cytochrome C protein expression were decreased 53% and 39% respectively after IL6 overexpression. These results show oxidative capacity in wasting skeletal muscle is reduced in both oxidative and glycolytic muscle and IL6 overexpression can reduce muscle oxidative capacity. Funded by R01CA12124901A2

published proceedings

  • The FASEB Journal

author list (cited authors)

  • White, J. P., Sato, S., Baltgalvis, K. A., Baynes, J. W., & Carson, J. A.

complete list of authors

  • White, James P||Sato, Shuichi||Baltgalvis, Kristen A||Baynes, John W||Carson, James A

publisher