α-Ionone attenuates high-fat diet-induced skeletal muscle wasting in mice via activation of cAMP signaling

Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacological therapy. Our aim was to investigate the potential of -ionone, a naturally occurring flavoring agent, in preventing muscle atrophy and to delineate the mechanisms involved. We found that -ionone not only stimulated myogenesis but also attenuated palmitic-acid-induced atrophy of cultured skeletal myotubes, as evidenced by an increased myotube diameter and length, fusion index, and cellular protein content. These beneficial actions of -ionone were abrogated by cAMP inhibitor. The antiatrophic effects of -ionone on cultured myotubes were confirmed in a corresponding mouse model. The skeletal muscle mass, muscle protein content, myofiber diameter, and muscle strength were greater in -ionone-treated mice than in untreated animals fed high-fat diet. Furthermore, -ionone increased cAMP concentration and enhanced its downstream PKA-CREB signaling in skeletal muscle of mice fed high-fat diet. Thus, -ionone is a promising agent that may enhance skeletal muscle mass and strength.