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Exercise limitation, muscle atrophy and increased angiopoietin mRNA in a mouse model of pulmonary TNFa induced inflammation
Author(s) -
Tang Kechun,
Wagner Peter D,
Breen Ellen C
Publication year - 2010
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.24.1_supplement.801.19
Subject(s) - skeletal muscle , inflammation , tumor necrosis factor alpha , medicine , endocrinology , muscle atrophy , soleus muscle , atrophy , systemic inflammation
Many chronic inflammatory diseases exhibit high circulating TNFa and skeletal muscle weakness. In this study, a mouse model of chronic pulmonary inflammation due to SP‐C driven TNFa overexpression was used to evaluate the effects of systemic TNFa on exercise capacity and locomotor skeletal muscle expression of atrophy and angiogenic genes. SP‐C/TNFa (+/−) mice (female, 6–8 months of age) had a 5.7‐fold increase in serum TNFa levels compared to littermate controls (29.6±9.6 vs. 5.2±3.5 pg/ml, p<0.001), reduced body weight (25.9±3.3 vs. 32.0±4.6 g, p=0.028, n=4), soleus mass (7.7±1.2 vs. 9.6±2.2 mg, p=0.021) and treadmill running endurance (60±9 vs. 81±11 min, p=0.016). In the soleus, PGC‐1a mRNA levels, measured by real time RT‐PCR, were decreased in the TNF(+/−) mice compared to control (1.6±0.4 vs. 3.1±1.4 units, p=0.014), and angiopoieitn‐1 mRNA was increased (51.5±15.9 vs. 10.0±6.3 units, p<0.001). These data suggest (1) prolonged high systemic TNFa levels alter skeletal muscle metabolism and function; (2) PGC‐1a, an important metabolic regulator, may be a key factor in inflammation associated muscle atrophy; (3) TNFa regulation of muscle angiopoietin‐1 has a potential role in protecting vascular integrity in chronic systemic inflammatory conditions. NIH/NHLBI 1 P01 HL091830‐01A1