Reduced REDD1 expression contributes to activation of mTORC1 following electrically induced muscle contraction

Abstract

Regulated in DNA damage and development 1 (REDD1) is a repressor of mTOR complex 1 (mTORC1) signaling. In humans, REDD1 mRNA expression in skeletal muscle is repressed following resistance exercise in association with activation of mTORC1. However, whether REDD1 protein expression is also reduced after exercise and if so to what extent the loss contributes to exercise-induced activation of mTORC1 is unknown. Thus, the purpose of the present study was to examine the role of REDD1 in governing the response of mTORC1 and protein synthesis to a single bout of muscle contractions. Eccentric contractions of the tibialis anterior were elicited via electrical stimulation of the sciatic nerve in male mice in either the fasted or fed state or in fasted wild-type or REDD1-null mice. Four hours postcontractions, mTORC1 signaling and protein synthesis were elevated in fasted mice in association with repressed REDD1 expression relative to nonstimulated controls. Feeding coupled with contractions further elevated mTORC1 signaling, whereas REDD1 protein expression was repressed compared with either feeding or contractions alone. Basal mTORC1 signaling and protein synthesis were elevated in REDD1-null compared with wild-type mice. The magnitude of the increase in mTORC1 signaling was similar in both wild-type and REDD1-null mice, but, unlike wild-type mice, muscle contractions did not stimulate protein synthesis in mice deficient for REDD1, presumably because basal rates were already elevated. Overall, the data demonstrate that REDD1 expression contributes to the modulation of mTORC1 signaling following feeding- and contraction-induced activation of the pathway.