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Inflammatory Cytokine IL‐6 and Cachectic Muscle Oxidative Capacity
Author(s) -
White James P,
Sato Shuichi,
Baltgalvis Kristen A,
Baynes John W,
Carson James A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.508.8
Subject(s) - cachexia , wasting , endocrinology , medicine , skeletal muscle , oxidative phosphorylation , glycolysis , gastrocnemius muscle , biology , mitochondrion , cytokine , inflammation , cancer , biochemistry , metabolism
Cancer cachexia is a condition of severe wasting of both skeletal muscle and adipose tissue. Circulating inflammatory cytokine IL‐6 can regulate the development of cachexia in the Apc Min/+ mouse, a model of colorectal cancer. The purpose of this study was to determine the effects of cancer cachexia and IL‐6 over‐expression on wasting skeletal muscle oxidative capacity. Gastrocnemius (GAST) muscle mitochondrial number, mitochondrial proteins and PGC‐1α mRNA expression were quantified. Apc Min/+ mice were stratified by cachexia severity. The GAST muscle was sectioned into red (oxidative) and white (glycolytic) portions to determine phenotype specific wasting. IL‐6 was over‐expressed in a subset of Apc Min/+ 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 PGC‐1α mRNA expression approximately 40% in severely wasting muscle. IL‐6 over‐expression resulted in a 63% decrease in PGC‐1α protein expression. Cox IV and Cytochrome C protein expression were decreased 53% and 39% respectively after IL‐6 over‐expression. These results show oxidative capacity in wasting skeletal muscle is reduced in both oxidative and glycolytic muscle and IL‐6 over‐expression can reduce muscle oxidative capacity. Funded by R01CA121249‐01A2