Integrative effects of resistance training and endurance training on mitochondrial remodeling in skeletal muscle.

Resistance training activates mammalian target of rapamycin (mTOR) pathway of hypertrophy for strength gain, while endurance training increases peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway of mitochondrial biogenesis benefiting oxidative phosphorylation. The conventional view suggests that resistance training-induced hypertrophy signaling interferes with endurance training-induced mitochondrial remodeling. However, this idea has been challenged because acute leg press and knee extension in humans enhance both muscle hypertrophy and mitochondrial remodeling signals. Thus, we first examined the muscle mitochondrial remodeling and hypertrophy signals with endurance training and resistance training, respectively. In addition, we discussed the influence of resistance training on muscle mitochondria, demonstrating that the PGC-1α-mediated muscle mitochondrial adaptation and hypertrophy occur simultaneously. The second aim was to discuss the integrative effects of concurrent training, which consists of endurance and resistance training sessions on mitochondrial remodeling. The study found that the resistance training component does not reduce muscle mitochondrial remodeling signals in concurrent training. On the contrary, concurrent training has the potential to amplify skeletal muscle mitochondrial biogenesis compared to a single exercise model. Concurrent training involving differential sequences of resistance and endurance training may result in varied mitochondrial biogenesis signals, which should be linked to the pre-activation of mTOR or PGC-1α signaling. Our review proposed a mechanism for mTOR signaling that promotes PGC-1α signaling through unidentified pathways. This mechanism may be account for the superior muscle mitochondrial remodeling change following the concurrent training. Our review suggested an interaction between resistance training and endurance training in skeletal muscle mitochondrial adaptation.

Resistance Training Improves Hypertrophic and Mitochondrial Adaptation in Skeletal Muscle.

Resistance training is employed for pursuing muscle strength characterized by activation of mammalian target of rapamycin (mTOR)-mediated hypertrophic signaling for protein production. Endurance training elevates peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling of mitochondrial adaptations for oxidative phosphorylation. Now, emerging evidence suggests that, like endurance training, resistance training also elicits profound effects on mitochondrial adaptations in skeletal muscle, which means that resistance training yields both strength and endurance phenotypes in myofibers, which has treatment value for the muscle loss and poor aerobic capacity in humans. Our review outlines a brief overview of muscle hypertrophic signals with resistance training, and focuses on the effects of resistance training on mitochondrial biogenesis and respiration in skeletal muscle. This study provides novel insights into the therapeutic strategy of resistance training for the metabolically dysfunctional individuals with declined mitochondrial function.

Hypoxic training upregulates mitochondrial turnover and angiogenesis of skeletal muscle in mice.

AIMS: Hypoxic training promotes human cardiopulmonary function and exercise performance efficiently, but the myocellular mechanism has been less studied. We aimed to examine the effects of hypoxic trainings on mitochondrial turnover and vascular remodeling of skeletal muscle. MAIN METHODS: C57BL/6 J mice were divided into control, hypoxic exposure, exercise training, "live high-train low" (LHTL), and "live low-train high" (LLTH) groups (n = 8/group). Western blot and immunohistochemistry were used to evaluate mitochondrial turnover of gastrocnemius and angiogenesis of quadriceps after six weeks interventions. KEY FINDINGS: Compared with control group, both LHTL and LLTH increased phosphorylation levels of p38 MAPK markedly (p < 0.05). LLTH also elevated PGC-1α protein expression significantly (p < 0.05). All interventions did not influence Bnip3 and Drp-1 proteins levels (p > 0.05), while LLTH enhanced Parkin and Mff protein contents significantly (p < 0.05). Immunohistochemical analysis showed both LHTL and LLTH promoted CD31 and VEGF expressions (p < 0.05). ATP content, citrate synthase activities of gastrocnemius were robustly elevated in LHTL and LLTH groups (p < 0.01). The exercise training increased Mff protein and ATP content in gastrocnemius as well as VEGF expression in quadriceps (p < 0.05). The hypoxic exposure also increased ATP content, citrate synthase, and ATP synthase activities in gastrocnemius as well as VEGF expression in quadriceps (p < 0.01). SIGNIFICANCE: Our results suggested that hypoxic trainings, especially LLTH, promoted mitochondrial turnover and angiogenesis of skeletal muscle, which may be an underlying mechanism of hypoxic training-induced exercise capacity.

[Research advances in relationship between mitochondrial dynamics and cellular energy metabolism and exercise intervention].

Mitochondrial dynamics, involving mitochondrial fusion, fission and autophagy, plays an important role in maintaining cellular physiological function and homeostasis. Mitochondria are the "energy plant" of human body, so the changes of mitochondrial fusion, division and autophagy are important for cell respiration and energy production. On the other hand, energy metabolism influences mitochondrial dynamics in turn. This paper reviewed the recent advances in studies on the relationship between energy metabolism and the proteins regulating mitochondrial fusion, fission and autophagy. The association of mitochondrial dynamics with electron chain complex expression, oxidative phosphorylation and ATP synthesis upon exercise intervention will provide theoretical references for the further studies in sports training and disease intervention.

[Effects of different intensity exercise training on apoptosis-related microRNAs and the targeted proteins in cardiomyocytes].

OBJECTIVE: To detect the levels of miR-1, miR-21 and their targeted proteins in hearts of mice after different exercise training, and discuss potential molecular mechanism. METHODS: Male C57BL/6 mice were randomly divided to 3 groups:sedentary (SE), exercise training 1(ET1) and exercise training 2 (ET2). SE did not do any exercise; ET1 undertook swimming training for 8 weeks, once a day, 5 days/week. Swimming 30 min in the 1st week, and the duration was increased 10 min per week to 90 min and maintained in the 7th and 8th week. ET2 performed the same work as ET1 and switched to twice a day by the end of the 5th week. TUNEL assay was applied to test myocardial apoptosis. Western blot and RT-PCR were used to detect proteins and miRs levels respectively. RESULTS: Compared with SE, in ET1, myocardial apoptosis and miR-1 level did not change, but its targeted protein Bcl-2 increased significantly(P<0.01). miR-21 and its targeted protein PDCD4 did not change significantly. In ET2, myocardial apoptosis and miR-1 level were decreased significantly(P<0.05). Bcl-2 was increased significantly(P<0.01). miR-21 also increased significantly (P<0.05), but PDCD4 did not decrease significantly. CONCLUSIONS: Exercise training in ET2 other than ET1 could down-regulate myocardial apoptosis. Alterations of miR-1 and Bcl-2 may be responsible for this cardioprotection. PDCD4 is not sensitive to exercise training, it is likely that miR-21 and other targeted proteins participate in exercise-regulative apoptosis.

[Effects of exercise training on myocardial mitochondrial miR-499-CaN-Drp-1 apoptotic pathway in mice].

OBJECTIVE: To detect the levels of miR-499 and relative proteins in hearts of mice after exercise training, and investigate the mechanism of exercise-regulative apoptosis. METHODS: Male C57BL/6 mice were randomly divided into 3 groups( n = 14): sedentary (SE), exercise training 1 (ET1) and exercise training 2 (ET2) group. SE did not do any exercise. ET1 performed swimming training for 8 weeks. ET2 performed the same work as ET1 until the 5th week. Then, mice trained twice a day until the end of training. TUNEL assay was applied to test myocardial apoptosis, RT-PCR and Western blot were used to detect miR-499 and proteins levels respectively. RESULTS: Compared with SE, stress in ET1 failed to affect apoptotic index (AI) and miR-499-CaN-Drp-1 pathway (P > 0.05). In contrast, exercise load in ET2 increased miR-499 level, decreased Drp-1 level and AI with statistical significance respectively (P < 0.05), but neither CaN expression nor CaN activity was changed significantly (P > 0.05). CONCLUSION: Swimming training can inhibit myocardial apoptosis, and the decrease in Drp-l may be responsible for the reduced myocardial apoptosis. CaN, the upstream protein, does not participate in exercise-regulative apoptosis.

Relationship between thioredoxin-interacting protein (TXNIP) and islet ß-cell dysfunction in patients with impaired glucose tolerance and hypertriglyceridemia.

AIMS: To study the relationship between thioredoxin-interacting protein (TXNIP) and pancreatic ß-cell function in patients with impaired glucose regulation and patients with both impaired glucose regulation and hypertriglyceridemia. METHODS: We analyzed a population of 90 patients with impaired glucose regulation (IGR), 87 patients with IGR and hypertriglyceridemia, and 90 subjects with normal glucose tolerance (NGT). The levels of plasma TXNIP, a regulator of cellular oxidative stress, were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was used to evaluate insulin resistance in all subjects. In addition, two factors (HOMA for ß-cell function [HOMA-ß]) and first-phase insulin response [FPIR]) were used to evaluate pancreatic ß-cell function. The correlations between the plasma levels of TXNIP, insulin resistance, and islet ß-cell dysfunction were analyzed using Pearson's correlation analysis. RESULTS: Compared with NGT, patients with IGR had significantly lower HOMA-ß and FPIR, and higher plasma levels of TXNIP. Compared with the IGR group, patients with both IGR and hypertriglyceridemia had significantly lower HOMA-ß and FPIR, and higher plasma levels of TXNIP. There was also a negative correlation between TXNIP and HOMA-ß or FPIR, and a positive correlation between TXNIP and HOMA-IR. CONCLUSIONS: These data showed that the level of TXNIP is increased in patients with IGR and patients with both IGR and hypertriglyceridemia, islet ß-cell dysfunction was related to the increased TXNIP in IGR patients.

[Effects of aerobic exercise training on antihypertension and expressions of VEGF, eNOS of skeletal muscle in spontaneous hypertensive rats].

OBJECTIVE: To investigate effects of exercise training on vascular regulators and discuss its antihypertensive mechanism. METHODS: Rats were divided into three groups (n = 7): spontaneous hypertensive rats control group (SHR-C), training group (SHR-T) and normotensive wistar-kyoto control group (WKY-C). Aerobic exercise consisted of 10 weeks of swimming training for 5 days/week. Exercise duration was 40 min in the first week, then 50 min in the second week, from the third week to the end of training, duration was maintained at 60 min. After training, vascular endothelial growth factor (VEGF) and other biomarkers in soleus were measured by RT-PCR and immunoblotting. RESULTS: VEGF and endothelial NO synthase (eNOS) in SHR-C were lower than that in WKY-C (P < 0.05). Blood pressure in SHR-C and SHR-T were higher than that in WKY-C before training; After training, compared with SHR-C, VEGFR2, eNOS, VEGF and VEGF mRNA increased significantly in SHR-T paralleled with marked decreases in blood pressure and heart rate respectively (P < 0.05, P < 0.01). CONCLUSION: Aerobic exercise training lowered the blood pressure in spontaneous hypertensive rats, and promoted VEGF mRNA level and expressions of VEGF, VEGFR2 and eNOS. The up-regulations of these vascular regulators could benefit angiogenesis and contribute to the antihypertensive effects.

[Effects of HiLo for two weeks on erythrocyte immune adhesion and leukocyte count of swimmers].

OBJECTIVE: To investigate the effects of living high-training low (HiLo) on innate immunity in blood of elite swimmers. METHODS: Six female swimmers undertook HiLo for two weeks, erythrocyte adhesion function and counts of leukocyte were tested in different time of training period. RESULTS: Red blood cell C3b receptor ring rate (RBC-C3bRR) decreased and red blood cell immune complex matter ring rate (RBC-ICR) increased significantly (P < 0.05), the two markers returned to base line 1 week after training. Counts of leukocyte and granulocyte decreased significantly (P < 0.05), and they recovered 1 week after training; Counts of lymphocyte and monocyte decreased without significance during training and did not recovered after training. CONCLUSION: Immunity of erythrocyte and granulocyte decreased quickly, but lymphocyte and monocyte recovered slowly, swimmers were adaptive to the training.