Abstract

Toll-like receptor 4 (TLR4), a receptor of the innate immune system, and TNF-α converting enzyme (TACE), a metalloproteinase involved in the processing of the inflammatory cytokine TNF-α, have been reported to be elevated in inflammatory-related diseases such as cardiovascular disease and type II diabetes. Both higher physical activity level (PA) and lower body fat percentage are associated with decreased disease risk and inflammation. However, the mechanisms underlying the anti-inflammatory effects of physical activity and lower body fat percentage are not clearly defined. The PURPOSE: of this study was to determine if associations exist among PA, body composition, and the pro-inflammatory proteins, TLR4 and TACE in the skeletal muscle of older adults. METHODS: In 26 subjects (M/F = 9/17, age=68±4y, BMI=26±3 kg·m-2) self-reported PA (Community Healthy Activities Model for Seniors, CHAMPS), estimated maximal oxygen consumption (YMCA cycle ergometer test), and body composition (air plethysmography) were measured. TLR4 and TACE were measured in skeletal muscle biopsies (vastus lateralis) using western blot analyses. Pearson product–moment correlations were run between variables. Significance was set to p< 0.05. RESULTS: The mean PA and VO2max values were 1633±1160 kcal·wk-1 and 30±6 ml·kg-1·min-1 respectively. There was no significant correlation between TLR4 and PA. There were significant correlations between %body fat and skeletal muscle TLR4 (r=0.519, p= 0.007) and TLR4 and TACE (r= 0.542, p = 0.03). There was a trend for a significant correlation between TACE and BF% (r= 0.364, p= 0.08). CONCLUSIONS: These preliminary data do not show a correlation between self-reported PA and TLR4 or TACE in skeletal muscle from healthy older adults. However, positive correlations were found between skeletal muscle TLR4 and BF%. Skeletal muscle TLR4 expression and to a lesser extent body fat percentage were correlated with TNF-α converting enzyme (TACE). Thus, elevated skeletal muscle expression of TLR4 and TACE may underlie reports indicating that increased adiposity is associated with elevated inflammation and disease risk.

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