Open AccessThe effect of exercise on IL‐6‐induced cachexia in the Apc Min /+ mouse
Author(s) -
Puppa Melissa J.,
White James P.,
Velázquez Kandy T.,
Baltgalvis Kristen A.,
Sato Shuichi,
Baynes John W.,
Carson James A.
Publication year - 2012
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1007/s13539-011-0047-1
Subject(s) - cachexia , endocrinology , medicine , inflammation , wasting , skeletal muscle , ampk , protein kinase b , adipose tissue , systemic inflammation , physical exercise , weight loss , biology , obesity , phosphorylation , cancer , protein kinase a , biochemistry
Background Cachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL‐6 accelerates cachexia in the Apc Min/+ mouse, but does not induce wasting in control C57BL/6 mice. With many chronic diseases, chronic inflammation and metabolic dysfunction can be improved with moderate exercise. A direct effect of regular moderate exercise on the prevention of IL‐6‐induced cachexia in the Apc Min/+ mouse has not been investigated. The purpose of this study was to assess the effects of exercise on the development of cachexia in the Apc Min/+ mouse. Methods Mice were randomly assigned to moderate treadmill exercise (18 m/min, 1 h, 6 days/week, 5% grade) or cage control (CC) groups from 6 to 14 weeks of age. At 12 weeks of age, mice were electroporated with either IL‐6‐containing or control plasmid into the quadriceps muscle. Mice were killed after 2 weeks of systemic IL‐6 overexpression or control treatment. Results IL‐6 overexpression induced an 8% loss in body weight in CC mice, which was significantly attenuated by exercise. IL‐6 overexpression in CC mice increased fasting insulin and triglyceride levels, which were normalized by exercise, and associated with increased oxidative capacity, an induction of AKT signaling, and a repression of AMPK signaling in muscle. These exercise‐induced changes occurred despite elevated inflammatory signaling in skeletal muscle. Conclusion We conclude that moderate‐intensity exercise can attenuate IL‐6‐dependent cachexia in Apc Min/+ mice, independent of changes in IL‐6 concentration and muscle inflammatory signaling. The exercise effect was associated with improved insulin sensitivity and improved energy status in the muscle.