gamma-Oryzanol Improves Exercise Endurance and Muscle Strength by Upregulating PPAR delta and ERR gamma Activity in Aged Mice

Abstract

Scope: gamma-Oryzanol, a well-known antioxidant, has been used by body builders and athletes to boost strength and increase muscle gain, without major side effects. However, the effect of gamma-Oryzanol on sarcopenia and the underlying molecular mechanism is poorly understood. Results: Aged mice fed with the gamma-Oryzanol diet do not show significant changes in muscle weight, but show increased running endurance as well as improved grip strength. The expression and activity of PPAR delta and ERR gamma are increased in skeletal muscle of gamma-Oryzanol supplemented mice. gamma-Oryzanol upregulates oxidative muscle fibers by MEF2 transcription factor, and PGC-1 alpha and ERR alpha expressions. Fatty acid oxidation related genes and mitochondria biogenesis are upregulated by gamma-Oryzanol. In addition, gamma-Oryzanol inhibits TGF-beta-Smad-NADPH oxidase 4 pathway and inflammatory cytokines such as TNF-alpha, IL-1 beta, IL-6, and p65 NF-kappa B subunit, which cause skeletal muscle weakness. Collectively, gamma-Oryzanol attenuates muscle weakness pathway and increases oxidative capacity by increasing PPAR delta and ERR gamma activity, which contributes to enhance strength and improve oxidative capacity in muscles, consequently enhancing exercise capacity in aged mice. Particularly, gamma-Oryzanol directly binds to PPAR delta. Conclusions: These are the first findings showing that gamma-Oryzanol enhances skeletal muscle function in aged mice by regulating PPAR delta and ERR gamma activi without muscle gain.