Serum levels and muscle expression of the chemokine CXC motif ligand 1 (CXCL-1) increase markedly in response to exercise in mice. As several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expression of muscle-derived CXCL-1 on systemic and intramuscular metabolic parameters, with focus on fatty acid oxidation and oxidative metabolism in skeletal muscle. By overexpression of CXCL-1 in the tibialis cranialis muscle in mice, significant elevations in muscle and serum CXCL-1 within a physiological range were obtained. At 3 months of high-fat feeding, visceral and subcutaneous fat mass were 32.4% (P < 0.01) and 22.4% (P < 0.05) lower in CXCL-1 overexpressing mice respectively compared to control mice. Also chow-fed CXCL-transfected mice had 35.4% (P < 0.05) lower visceral fat mass and 33.4% (P < 0.05) lower subcutaneous fat mass compared to chow-fed control mice. These reductions in accumulation of adipose tissue were accompanied by improved glucose tolerance and insulin sensitivity. Furthermore, in CXCL-1 transfected muscles muscular ex vivo fatty acid oxidation was significantly enhanced compared to control muscles (chow-fed: 2.2 fold, P<0.05 and high-fat-fed: 2.0 fold, P<0.05) and also showed increased expression levels of major fatty acid oxidation genes (CD36, CPT-1 and HADH). Finally CXCL-1 expression was associated with increased muscle mRNA expression of VEGF and CD31, suggesting a role of CXCL-1 in muscle angiogenesis. In conclusion, our data shows that overexpression of CXCL-1 within a physiological range attenuates diet-induced obesity, likely mediated through a CXCL-1-induced improvement of fatty acid oxidation and oxidative capacity in skeletal muscle tissue.
- Fatty acid oxidation
- Copyright © 2011, American Journal of Physiology - Endocrinology and Metabolism