Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc Min/+ mouse
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Interleukin-6 (IL-6) is necessary for cachexia in Apc Min/+ mice, but the mechanisms inducing this myofiber wasting have not been established. The purpose of this study was to examine gastrocnemius muscle wasting in the Apc Min/+ mouse and to determine IL-6 regulated mechanisms contributing to muscle loss. Gastrocnemius type IIB mean fiber cross-sectional area (CSA) from Apc Min/+ mice decreased 32% between 13 and 22 weeks of age. Apc Min/+ mice lacking IL-6 did not have type IIB fiber atrophy, while overexpression of circulating IL-6 exacerbated the loss of type IIB fiber CSA in Apc Min/+ mice. Muscle Atrogin-I mRNA expression was induced at least ninefold at 18 and 22 weeks of age compared to 13-week-old mice. Atrogin-I gene expression was also induced by overexpression of circulating IL-6. These data suggest that high circulating IL-6 levels induce type IIB fiber CSA loss in Apc Min/+ mice, and circulating IL-6 is sufficient to regulate Atrogin-I gene expression in cachectic mice.
KeywordsSkeletal muscle Cytokine Interleukin Inflammation Intestine Colon
The authors would like to thank Tia Davis, Joseph McClung, and April Wilson for technical assistance. The research described in this report was supported by the National Institutes of Health (NIH) Grant P20 RR-017698 from the National Center for Research Resources. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
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