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α‐Cedrene, a Newly Identified Ligand of MOR23, Increases Skeletal Muscle Mass and Strength
Author(s) -
Tong Tao,
Kim Minji,
Park Taesun
Publication year - 2018
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201800173
Subject(s) - myogenesis , skeletal muscle , medicine , endocrinology , muscle hypertrophy , chemistry , myocyte , biology , microbiology and biotechnology
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.