Skeletal muscle TLR4 and TACE are associated with body fat percentage in older adults.

Elevated skeletal muscle expression of toll-like receptor 4 (TLR4) has been linked to increased inflammation in clinical populations. TNFα converting enzyme (TACE), which cleaves membrane-bound TNFα (mTNFα) to its soluble (sTNFα) and more bioactive form, has been linked to chronic disease. In contrast, higher physical activity level is associated with decreased chronic disease risk and inflammation. The purpose of the present study was to examine the relationship between physical activity and skeletal muscle TLR4, TACE, and TNFα in older adults. In 26 older adults (age = 68 ± 4 years, body mass index = 26 ± 3 kg·m(-2)), self-reported physical activity (kcal·week(-1)), estimated maximal oxygen consumption, and body composition (air plethysmography) were measured. TLR4, TACE, mTNFα, and sTNFα were measured in skeletal muscle biopsies (vastus lateralis) using western blot analyses. Pearson product-moment correlations were run between variables. Significance was set at p < 0.05. Skeletal muscle TACE was directly associated with sTNFα (r = 0.53, p < 0.01). Linear regression modeling showed that mTNFα and TACE expression were predictive of sTNFα expression. No correlations were observed between physical activity and TLR4, TACE, or sTNFα. Percent body fat was directly associated with skeletal muscle TLR4 (r = 0.52, p < 0.01) and TACE (r = 0.50, p < 0.01), whereas fasting blood glucose was directly associated with TACE and sTNFα. In conclusion, we found that percent body fat was directly associated with TLR4 and TACE expression in skeletal muscle of older adults. These findings suggest that elevated skeletal muscle expression of TLR4 and TACE may contribute to the augmented inflammation and chronic disease risk observed with increased adiposity.