Age-dependent increase in angiopoietin-like protein 2 accelerates skeletal muscle loss in mice.

Skeletal muscle atrophy, or sarcopenia, is commonly observed in older individuals and in those with chronic disease and is associated with decreased quality of life. There is recent medical and broad concern that sarcopenia is rapidly increasing worldwide as populations age. At present, strength training is the only effective intervention for preventing sarcopenia development, but it is not known how this exercise regimen counteracts this condition. Here, we report that expression of the inflammatory mediator angiopoietin-like protein 2 (ANGPTL2) increases in skeletal muscle of aging mice. Moreover, in addition to exhibiting increased inflammation and accumulation of reactive oxygen species (ROS), denervated atrophic skeletal muscles in a mouse model of denervation-induced muscle atrophy had increased ANGPTL2 expression. Interestingly, mice with a skeletal myocyte-specific Angptl2 knockout had attenuated inflammation and ROS accumulation in denervated skeletal muscle, accompanied by increased satellite cell activity and inhibition of muscular atrophy compared with mice harboring wildtype Angptl2 Moreover, consistent with these phenotypes, wildtype mice undergoing exercise training displayed decreased ANGPTL2 expression in skeletal muscle. In conclusion, ANGPTL2 up-regulation in skeletal myocytes accelerates muscle atrophy, and exercise-induced attenuation of ANGPTL2 expression in those tissues may partially explain how exercise training prevents sarcopenia.