Rapamycin does not prevent increases in myofibrillar or mitochondrial protein synthesis following endurance exercise

Abstract

Key pointsr Previous studies have shown that endurance exercise increases myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in skeletal muscle.r The mechanistic target of rapamycin (mTOR) is considered to be a key intracellular nutrient-sensing protein complex, which activates MyoPS in response to anabolic stimuli.r Little is known regarding the regulation of MyoPS and MitoPS in response to endurance exercise.r In the present study, we show that MyoPS and MitoPS increase in skeletal muscle following endurance exercise, despite suppression of mTORC1 during the post-exercise recovery period.r Our data suggests that mTORC1 independent processes regulate both MyoPS and MitoPS following acute endurance exercise. AbstractThe present study aimed to investigate the role of the mechanistic target of rapamycin complex 1 (mTORC1) in the regulation of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis following endurance exercise. Forty-two female C57BL/6 mice performed 1 h of treadmill running (18 m min −1 ; 5°grade), 1 h after I.P. administration of rapamycin (1.5 mg · kg −1 ) or vehicle. To quantify skeletal muscle protein fractional synthesis rates, a flooding dose (50 mg · kg −1 ) of L-[ring-13 C 6 ]phenylalanine was administered via I.P. injection. Blood and gastrocnemius muscle were collected in non-exercised control mice, as well as at 0.5, 3 and 6 h after completing exercise (n = 4 per time point). Skeletal muscle MyoPS and MitoPS were determined by measuring isotope incorporation in their respective protein pools. Activation of the mTORC1-signalling cascade was measured via direct kinase activity assay and immunoblotting, whereas genes related to mitochondrial biogenesis were measured via a quantitative RT-PCR. MyoPS increased rapidly in the vehicle group post-exercise and remained elevated for 6 h, whereas this response was transiently blunted (30 min post-exercise) by rapamycin. By contrast, MitoPS was unaffected by rapamycin, and was increased over the entire post-exercise recovery period in both groups (P < 0.05). Despite rapid increases in both MyoPS and MitoPS, mTORC1 activation was suppressed in both groups post-exercise for the entire 6 h recovery period. Peroxisome proliferator activated receptor-γ coactivator-1α, pyruvate dehydrogenase kinase 4 and mitochondrial transcription factor A mRNA increased post-exercise (P < 0.05) * These authors contributed equally to this work. and this response was augmented by rapamycin (P < 0.05). Collectively, these data suggest that endurance exercise stimulates MyoPS and MitoPS in skeletal muscle independently of mTORC1 activation.

Increased Skeletal Muscle GLUT4 Expression in Obese Mice After Voluntary Wheel Running Exercise Is Posttranscriptional

“…Together, the data show that both HFD and VWR have distinct effects on phosphorylation of these downstream mTORC1 substrates. Furthermore, the findings support the notion that S6K and 4E-BP1 phosphorylation states undergo differential regulation depending on environmental and physiological conditions, including response to HFD and VWR exercise (43–46). …”

Intake of branched-chain or essential amino acids attenuates the elevation in muscle levels of PGC-1α4 mRNA caused by resistance exercise

“…However, in a recent study, administration of rapamycin to mice was found to amplify the increase in PGC-1␣ mRNA caused by 1 h of running, suggesting an inverse relationship between mTORC1 activity and PGC-1␣ (23). Nonetheless, the lack of any effect of leucine alone on the PGC-1␣4 response, despite its stimulatory effect on mTORC1 signaling ( Fig.…”

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

“…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).…”

“…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).…”