mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle

Ogasawara, Riki; Kobayashi, Kōji; Tsutaki, Arata; Lee, Kihyuk; Abe, Takashi; Fujita, Satoshi; Nakazato, Koichi; Ishii, Naokata

doi:10.1152/japplphysiol.01161.2012

Cited by 117 publications

(115 citation statements)

References 44 publications

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“…The voltage (ϳ30 V) and stimulation frequency (100 Hz) were adjusted to produce maximal isometric tension. In a previous study, we demonstrated that this exercise protocol induces significant muscle hypertrophy, simulating longterm training (50).…”

Section: Re Protocolmentioning

confidence: 77%

“…Western blotting analysis was performed as reported previously (50). In brief, muscle samples were homogenized with a Polytron homogenizer in a homogenization buffer containing 20 mM Tris·HCl (pH 7.5), 1% NP-40, 1% sodium deoxycholate, 1 mM EDTA, 1 mM EGTA, 150 mM NaCl, and protease and phosphatase inhibitor cocktail (Thermo Fisher Scientific).…”

Section: Western Blotting Analysismentioning

confidence: 99%

“…The well-known adaptive features of chronic muscle contraction include muscle hypertrophy and increased strength. These features are induced by high-intensity muscle contraction, such as that involved in resistance exercises (RE) (50,52). Other typical adaptations are increases in oxidative capacity and glucose uptake, which are induced by low-intensity, highvolume muscle contraction, such as that observed during endurance exercises (EE) (5,28,53).…”

mentioning

confidence: 99%

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The order of concurrent endurance and resistance exercise modifies mTOR signaling and protein synthesis in rat skeletal muscle

Ogasawara

Sato

Matsutani

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Ogasawara R, Sato K, Matsutani K, Nakazato K, Fujita S. The order of concurrent endurance and resistance exercise modifies mTOR signaling and protein synthesis in rat skeletal muscle. Am J Physiol Endocrinol Metab 306: E1155-E1162, 2014. First published April 1, 2014; doi:10.1152/ajpendo.00647.2013.-Concurrent training, a combination of endurance (EE) and resistance exercise (RE) performed in succession, may compromise the muscle hypertrophic adaptations induced by RE alone. However, little is known about the molecular signaling interactions underlying the changes in skeletal muscle adaptation during concurrent training. Here, we used an animal model to investigate whether EE before or after RE affects the molecular signaling associated with muscle protein synthesis, specifically the interaction between RE-induced mammalian target of rapamycin complex 1 (mTORC1) signaling and EE-induced AMP-activated protein kinase (AMPK) signaling. Male Sprague-Dawley rats were divided into five groups: an EE group (treadmill, 25 m/min, 60 min), an RE group (maximum isometric contraction via percutaneous electrical stimulation for 3 ϫ 10 s, 5 sets), an EE before RE group, an EE after RE group, and a nonexercise control group. Phosphorylation of p70S6K, a marker of mTORC1 activity, was significantly increased 3 h after RE in both the EE before RE and EE after RE groups, but the increase was smaller in latter. Furthermore, protein synthesis was greatly increased 6 h after RE in the EE before RE group. Increases in the phosphorylation of AMPK and Raptor were observed only in the EE after RE group. Akt and mTOR phosphorylation were increased in both groups, with no between-group differences. Our results suggest that the last bout of exercise dictates the molecular responses and that mTORC1 signaling induced by any prior bout of RE may be downregulated by a subsequent bout of EE. concurrent exercise; mammalian target of rapamycin complex 1; adenosine 5=-monophosphate-activated protein kinase; resistance exercise; endurance exercise SKELETAL MUSCLE IS A HIGHLY PLASTIC TISSUE that adapts differently to different stimuli, including various types of muscle contractions. Chronic muscle contraction induces diverse metabolic and morphological adaptations because of the cumulative effects of repeated bouts of exercise, and certain molecular and cellular responses lead to specific adaptations (3, 10, 47). The well-known adaptive features of chronic muscle contraction include muscle hypertrophy and increased strength. These features are induced by high-intensity muscle contraction, such as that involved in resistance exercises (RE) (50, 52). Other typical adaptations are increases in oxidative capacity and glucose uptake, which are induced by low-intensity, highvolume muscle contraction, such as that observed during endurance exercises (EE) (5, 28, 53).Concurrent training, a combination of EE and RE in succession, is used widely in exercise prescription to simultaneously improve muscular strength and cardiovascular function. Interestingly, ac...

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Section: Re Protocolmentioning

confidence: 77%

Section: Western Blotting Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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The order of concurrent endurance and resistance exercise modifies mTOR signaling and protein synthesis in rat skeletal muscle

Ogasawara

Sato

Matsutani

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Nutrition and exercise are well known to activate p70S6K (19,43). 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).…”

Section: Discussionmentioning

confidence: 97%

“…The mice were trained on a rodent treadmill (Osaka Microsystems, Osaka, Japan) for 30 min/d at 5-12 m/min over a period of 5 d for accustomization to the treadmill. Then, the mice ran on the treadmill for 45 42,24 h after the last bout of exercise, the animals were euthanized by blood collection from the inferior vena cava under isoflurane anesthesia after 4 h of fasting, and the gastrocnemius, soleus, extensor digitorum longus, epididymal fat, and liver were immediately removed. After being weighed, the tissues were rapidly frozen in liquid nitrogen and stored at Ϫ80˚C until analysis.…”

Section: Animals and Dietsmentioning

confidence: 99%

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

Takamura

Nomura

Uchiyama

et al. 2017

J Nutr Sci Vitaminol

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Summary Insulin resistance reduces insulin-induced muscle protein synthesis and accelerates muscle protein degradation. Ginseng ingestion has been reported to improve insulin resistance through the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We hypothesized that panaxatriol (PT) derived from ginseng in combination with aerobic exercise (EX) may further promote protein synthesis and suppress protein degradation, and subsequently maintain muscle mass through the amelioration of insulin resistance. KKAy insulin-resistant mice were divided into control, panaxatriol only (PT), exercise only (EX), and EXϩPT groups. EX and EXϩPT ran on the treadmill for 45 min at 15 m/min 5 d/wk for 6 wk. PT and EXϩPT groups were fed a standard diet containing 0.2% PT for 6 wk. Homeostasis model assessment for insulin resistance (HOMA-R) values was significantly improved after exercise for 6 wk. Moreover, EXϩPT mice showed improved HOMA-R as compared to EX mice. p70S6K phosphorylation after a 4 h fast was significantly higher in EX than in the non-exercise control, and it was higher in EXϩPT mice than in EX mice. Atrogin1 mRNA expression was significantly lower in EX than in the non-exercise control, and was significantly lowered further by PT treatment. EX and EXϩPT mice showed higher soleus muscle mass and cross-sectional area (CSA) of the soleus myofibers than control animals, with higher values noted for both parameters in EXϩPT than in EX. These results suggest that aerobic exercise and PT ingestion may contribute to maintain skeletal muscle mass through the amelioration of insulin resistance.

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Downhill Running Excessive Training Inhibits Hypertrophy in Mice Skeletal Muscles with Different Fiber Type Composition

et al. 2015

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The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80°C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type.

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mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle

Abstract: Ogasawara R, Kobayashi K, Tsutaki A, Lee K, Abe T, Fujita S, Nakazato K, Ishii N. mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle.

Cited by 117 publications

References 44 publications

The order of concurrent endurance and resistance exercise modifies mTOR signaling and protein synthesis in rat skeletal muscle

The order of concurrent endurance and resistance exercise modifies mTOR signaling and protein synthesis in rat skeletal muscle

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

Downhill Running Excessive Training Inhibits Hypertrophy in Mice Skeletal Muscles with Different Fiber Type Composition

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