Endurance exercise induces REDD1 expression and transiently decreases mTORC1 signaling in rat skeletal muscle

Abstract

Working muscle conserves adenosine triphosphate (ATP) for muscle contraction by attenuating protein synthesis through several different pathways. Regulated in development and DNA damage response 1 (REDD1) is one candidate protein that can itself attenuate muscle protein synthesis during muscle contraction. In this study, we investigated whether endurance exercise induces REDD1 expression in association with decreased mammalian target of rapamycin (mTOR) complex I (mTORC1) signaling and global protein synthesis in rat skeletal muscle. After overnight fasting, rats ran on a treadmill at a speed of 28 m/min for 60 min, and were killed before and immediately, 1, 3, 6, 12, and 24 h after exercise. REDD1 mRNA and corresponding protein levels increased rapidly immediately after exercise, and gradually decreased back to the basal level over a period of 6 h in the gastrocnemius muscle. Phosphorylation of mTOR Ser2448 and S6K1 Thr389 increased with the exercise, but diminished in 1–3 h into the recovery period after cessation of exercise. The rate of protein synthesis, as determined by the surface sensing of translation (SUnSET) method, was not altered by exercise in fasted muscle. These results suggest that REDD1 attenuates exercise‐induced mTORC1 signaling. This may be one mechanism responsible for blunting muscle protein synthesis during exercise and in the early postexercise recovery period.

Effects of Aerobic Exercise Combined with Panaxatriol Derived from Ginseng on Insulin Resistance and Skeletal Muscle Mass in Type 2 Diabetic Mice

“…Previous studies have reported that activation of p70S6K in rodent skeletal muscle following resistance exercise was maintained for 24 h after exercise (8,44,45). On the other hand activation of p70S6K in rodent skeletal muscle following aerobic exercise returned to baseline within 12 h after exercise (10,46,47). In the present study, p70S6K was activated 24 h after aerobic exercise, which was not consistent with previous studies.…”

“…Previous studies adopted a fasting time of 12-16 h (10,46,47), whereas the present study adopted a time of 4 h. Activation of p70S6K by nutrition intake has been reported to be maintained for 4 h (48,49). Therefore, activation of p70S6K in the present study may have reflected nutrition intake rather than aerobic exercise.…”

Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation

“…5D). A discrepancy between mTOR activation and increased steady state of protein synthesis has been reported by others (26). This result was in accordance with the absence of cardiac morphological changes observed in the absence of MLIP (Fig.…”

Emerging role for regulated in development and DNA damage 1 (REDD1) in the regulation of skeletal muscle metabolism

“…A single bout of treadmill aerobic exercise increases REDD1 mRNA and protein in the gastrocnemius of male rats as well as male and female mice (51,89,99). In mice, the increase in REDD1 protein appeared to coincide with repressed mTORC1 signaling, whereas in rats, mTORC1 signaling was increased in parallel with elevated REDD1 protein (51,99). In humans, a single 20-min bout of submaximal aerobic exercise on a cycle ergometer at an intensity of 1.2 W/kg (ϳ50% of the subjects' V O 2 max ) failed to change REDD1 protein in the vastus lateralis, wheereas mTORC1 signaling was blunted (81).…”

“…The role of REDD1 in regulating the nutrient-and contraction-induced stimulation of mTORC1 and protein synthesis is relatively well explored, whereas there is a paucity of consistent data pertaining to its role during aerobic exercise. A single bout of treadmill aerobic exercise increases REDD1 mRNA and protein in the gastrocnemius of male rats as well as male and female mice (51,89,99). In mice, the increase in REDD1 protein appeared to coincide with repressed mTORC1 signaling, whereas in rats, mTORC1 signaling was increased in parallel with elevated REDD1 protein (51,99).…”