Scope: Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. In this study, the effects of α-cedrene are tested, a natural ligand of mouse olfactory receptor 23 (MOR23) whose ectopic function regulating myogenesis on skeletal muscle growth was reported recently. Methods and results: α-Cedrene not only stimulated hypertrophy but also attenuated free fatty acid-induced atrophy of cultured skeletal myotubes, as evidenced by an increased myotube diameter, fusion index, and total cellular protein content. These hypertrophic and antiatrophic properties of α-cedrene in cultured myotubes were confirmed in corresponding mouse models. The skeletal muscle mass, total muscle protein content, average cross-sectional area of myofibers, and muscle strength were significantly greater in α-cedrene-treated mice compared with untreated animals during either a regular chow diet or high-fat diet. Receptor knockdown experiments using RNA interference in cultured skeletal myotubes revealed that the hypertrophic and antiatrophic properties of α-cedrene may be mediated by MOR23. Furthermore, α-cedrene induced the expression of MOR23 and enhanced its downstream cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA)–cyclic AMP-responsive element-binding protein (CREB) signaling in the skeletal muscle of mice fed chow or high-fat diet. Conclusions: α-Cedrene is a promising agent that may be applied to enhance the mass and strength of skeletal muscle.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea Grant (funded by the Korean Government; NRF-2016R1A2B4016189). T.T. and T.P. designed the study; T.T. and M.K. conducted the experiments; T.T. and M.K. analyzed the data; T.T. and T.P. wrote the manuscript.
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All Science Journal Classification (ASJC) codes
- Food Science