%0 Journal Article
%T IL-6 regulation on skeletal muscle mitochondrial remodeling during cancer cachexia in the ApcMin/+ mouse
%A James P White
%A Melissa J Puppa
%A Shuichi Sato
%A Song Gao
%A Robert L Price
%A John W Baynes
%A Matthew C Kostek
%A Lydia E Matesic
%A James A Carson
%J Skeletal Muscle
%D 2012
%I BioMed Central
%R 10.1186/2044-5040-2-14
%X ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL)-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts.Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1¦Á and fusion (Mfn1, Mfn2) protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1¦Á and fusion proteins were further suppressed, and fission protein (FIS1) was induced. IL-6 receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1¦Á, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1¦Á and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression induced. Exercise normalized these IL-6 induced effects. C2C12 myotubes administered IL-6 had increased FIS1 protein expression, increased oxidative stress, and reduced PGC-1¦Á gene expression without altered mitochondrial protein expression.Altered expression of proteins regulating mitochondrial biogenesis and fusion are early events in the initiation of cachexia regulated by IL-6, which precede the loss of muscle mitochondrial content. Furthermore, IL-6 induced mitochondrial remodeling and proteolysis can be rescued with moderate exercise training even in the presence of high circulating IL-6 levels.
%K FIS1
%K PGC-1¦Á
%K Exercise
%K IL-6r
%K MFN1
%K Cachexia
%K Mitochondria
%K Muscle
%K Autophagy
%U http://www.skeletalmusclejournal.com/content/2/1/14/abstract