Abstract
Chronic stress leads to hypothalamic-pituitary-adrenal axis dysfunction, increasing cortisol levels. Glucocorticoids (GCs) promote muscle degradation and inhibit muscle synthesis, eventually causing muscle atrophy. In this study, we aimed to evaluate whether rice germ supplemented with 30% γ-aminobutyric acid (RG) attenuates muscle atrophy in an animal model of chronic unpredictable mild stress (CUMS). We observed that CUMS raised the adrenal gland weight and serum adrenocorticotropic hormone (ACTH) and cortisol levels, and these effects were reversed by RG. CUMS also enhanced the expression of the GC receptor (GR) and GC-GR binding in the gastrocnemius muscle, which were attenuated by RG. The expression levels of muscle degradation-related signaling pathways, such as the Klf15, Redd-1, FoxO3a, Atrogin-1, and MuRF1 pathways, were enhanced by CUMS and attenuated by RG. Muscle synthesis-related signaling pathways, such as the IGF-1/AKT/mTOR/s6k/4E-BP1 pathway, were reduced by CUMS and enhanced by RG. Moreover, CUMS raised oxidative stress by enhancing the levels of iNOS and acetylated p53, which are involved in cell cycle arrest, whereas RG attenuated both iNOS and acetylated p53 levels. Cell proliferation in the gastrocnemius muscle was reduced by CUMS and enhanced by RG. The muscle weight, muscle fiber cross-sectional area, and grip strength were reduced by CUMS and enhanced by RG. Therefore, RG attenuated ACTH levels and cortisol-related muscle atrophy in CUMS animals.