Time-of-day effect of high-intensity muscle contraction on mTOR signaling and protein synthesis in mice.

Resistance exercise promotes muscle protein synthesis by activating mechanistic target of rapamycin (mTOR). The magnitude of muscle hypertrophy might differ depending on the timing of resistance exercise, but the molecular mechanism remains unclear. We aimed to define whether the time of day when muscles are contracted affects mTOR signaling and muscle protein synthesis. Adult male C57BL/6 J mice were housed under a 12 h/12 h light/dark cycle, and right gastrocnemius muscles were contracted using percutaneous electrical stimulation at 1, 7, 13, or 19 h after lights on. Contractions induced more phosphorylation of downstream targets of mTOR complex 1 (mTORC1) signaling such as S6K1 and rpS6 during the light (sleep), than the dark (active) phase, while expression of the negative regulator of mTORC1 that regulates development and DNA damage responses 1 (REDD1) was anti-phasic. Basal muscle protein synthesis in the sedentary leg was higher during the light, compared to the dark phase, while contraction-induced synthesis did not significantly vary throughout the day. Muscle hypertrophy is controlled by the balance between protein synthesis and degradation. Therefore, further studies are needed to elucidate the time-of-day effects of resistance exercise on muscle hypertrophy.