The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial.

Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual's motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).

A MUFA/carotenoid-rich oil ameliorated insulin resistance by improving inflammation and oxidative stress in obese rats.

Obesity is associated with low-grade inflammation and oxidative stress, leading to insulin resistance and type II diabetes. Caryocar brasiliense pulp oil (pequi oil - PO) is rich in oleic acid and carotenoids and positively implicated in regulating inflammation and oxidative stress. This study investigated PO's antioxidant and anti-inflammatory effects in a diet-induced obesity model. Male Wistar rats were allocated into three experimental groups: Control (CD), Western Diet (WD), and Western Diet, with 27% of lard switched by PO (WDP). Metabolic, inflammatory, and oxidative stress biomarkers were evaluated after 12 weeks of diet protocols in liver and adipose tissue. WDP rats gained less body mass and epididymal fat, had less hepatic fat infiltration, and were more glucose-tolerant and insulin-sensitive than WD (p < 0.05). In the liver, the WDP group had the highest non-enzymatic antioxidant capacity, SOD and GPx activities, CAT, SOD II, and HSP72 expression compared to WD (p < 0.05). Adipose tissue IL-6 and TNF were reduced, and IL-10 was increased in WDP compared to WD (p < 0.05). Our data suggest that the partial replacement of lard by PO in a Western diet prevented visceral fat accumulation and contributed to reducing inflammation in adipose tissue and liver oxidative stress, improving obesity-related insulin resistance.

Randomized Controlled Trial to Study the Acute Effects of Strength Exercise on Insulin Sensitivity in Obese Adults.

An acute session of strength exercise (SE) ameliorates insulin sensitivity (IS) for several hours; however, the effects of SE volume (i.e., number of sets) have not been studied thoroughly. Although it is intuitive that some SE is better than none, and more is better than some for the improvement of IS, high-volume sessions might be challenging for diseased populations to complete, especially obese adults, for whom even a brisk walk can be challenging. This protocol details a randomized clinical trial to assess the acute effects of SE on IS in obese adults. The inclusion criteria are body mass index >30 kg/m2, central obesity (waist circumference >88 cm and >102 cm for women and men, respectively), and age >40 years. Participants will be familiarized with the SE (7 exercises targeting major muscle groups) and then will perform three sessions in a randomized order: session 1 - high-volume session (3 sets/exercise); session 2 - low-volume session (1 set/exercise); session 3 - control session (no exercise). Diet will be controlled the day before and on the day of the sessions. Sessions will be completed at night, and an oral glucose tolerance test will be performed the next morning, from which several indexes of IS will be derived, such as the area under the curve (AUC) of glucose and insulin, the Matsuda index, the Cederholm index, the muscle IS index, and the Gutt index. Based on pilot studies, we expect ~15% improvement in IS (insulin AUC, and Matsuda and Cederholm indexes) after the high-volume session, and ~8% improvement after the low-volume session compared to the control session. This study will benefit individuals who find high-volume SE sessions challenging but still aim to improve their IS by investing 1/3 of their time and effort.

Intense Caloric Restriction from Birth Prevents Cardiovascular Aging in Rats.

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

Dose and time-response effect of photobiomodulation therapy on glycemic control in type 2 diabetic patients combined or not with hypoglycemic medicine: A randomized, crossover, double-blind, sham-controlled trial.

Photobiomodulation therapy (PBMt) combined or not with oral hypoglycemic medication has not been investigated in type 2 diabetes (T2DM) patients. All 10 T2DM patients were assessed randomly at 6 different occasions (3 with and 3 without regular oral hypoglycemic medication). Capillary glycemia was assessed after overnight fast (pre-prandial), 1 h postprandially (standardized meal, 338 kcal), and 30 min, 3 h, 6 h, 12 h post-PBMt (830 nm; 25 arrays of LEDs, 80 mW/array). Three doses (0 J-sham, 100 J, 240 J per site) were applied bilaterally on quadriceps femoris muscles, hamstrings, triceps surae, ventral upper arm and forearm; and randomly combined or not with oral hypoglicemic medication, totaling six different therapies applied for all 10 TDM2 patients (PBMt sham, PBMt 100 J, PBMt 240 J, PBMt sham + medication, PBMt 100 J + medication, PBMt 240 J + medication). Cardiac autonomic control was assessed by heart rate variability (HRV) indices. Without medication, there was reduction in glycemia after all PBMt doses, with 100 J as the best dose that persisted until 12 h and presented lower area under the curve (AUC). With medication, glycemia decreased similarly among doses. No differences between 100 J and sham + medication, but AUC was significantly lower after 100 J, suggesting better glycemic control. Low frequency component of HRV increased after sham + medication and 100 J, suggesting higher sympathetic activation. PBMt showed time- and dose-response effect to reduce glycemia in T2DM patients. Effects on HRV were consistent with glycemic control.

Superior cardiometabolic and cellular adaptive responses to multiple versus single daily sessions of high-intensity interval training in Wistar rats.

This study aimed to compare in rats the cardiometabolic and cellular adaptative responses to 8 weeks of high-intensity interval training (HIIT) performed in a single (1xHIIT) or three shorter daily sessions (3xHIIT). Male Wistar rats were assigned to untrained (n = 10), 1xHIIT (n = 10), and 3xHIIT (n = 10) groups. Both HIIT groups performed 15 min of a treadmill run five times per week for 8 weeks. The 1xHIIT performed single daily sessions of 15 min, and the 3xHIIT performed three daily sessions of 5 min with an interval of 4 h between sessions. Resting VO2 and VO2max were measured using a metabolic chamber; blood pressure and heart rate were measured by plethysmography; body composition was estimated by DEXA; Glucose and insulin tolerance tests were performed; after euthanasia, hearts, gastrocnemius, and visceral fat were harvested for analysis of cardiac function, histology, and morphology. Mitochondrial densities of the gastrocnemius and left ventricle muscles were determined by electron microscopy. 3xHIIT induced similar positive adaptative responses to 1xHIIT on resting VO2 and VO2max, cardiac function, and mitochondria density. 3xHIIT was superior to 1xHIIT in reducing visceral fat weight and adipocyte size and improving insulin tolerance. Multiple short daily bouts of HIIT may be superior to single HIIT daily sessions in improving cardiometabolic and cellular adaptations in rats.

Corrigendum: Modulation of leukocyte subsets mobilization in response to exercise by water immersion recovery.

[This corrects the article DOI: 10.3389/fphys.2022.867362.].

Modulation of Leukocyte Subsets Mobilization in Response to Exercise by Water Immersion Recovery.

Purpose: To investigate the effect of different water immersion temperatures on the kinetics of blood markers of skeletal muscle damage and the main leukocyte subpopulations. Methods: Eleven recreationally trained young men participated in four experimental sessions consisting of unilateral eccentric knee flexion and 90 min of treadmill running at 70% of peak oxygen uptake, followed by 15 min of water immersion recovery at 15, 28 or 38°C. In the control condition participants remained seated at room temperature. Four hours after exercise recovery, participants completed a performance test. Blood samples were obtained before and immediately after exercise, after immersion, immediately before and after the performance test and 24 h after exercise. The number of leukocyte populations and the percentage of lymphocyte and monocytes subsets, as well as the serum activity of creatine kinase and aspartate aminotransferase were determined. Results: Leukocytosis and increase in blood markers of skeletal muscle damage were observed after the exercise. Magnitude effect analysis indicated that post-exercise hot-water immersion likely reduced the exercise-induced lymphocytosis and monocytosis. Despite reduced monocyte count, recovery by 38°C immersion, as well as 28°C, likely increased the percentage of non-classical monocytes in the blood. The percentage of CD25+ cells in the CD4 T cell subpopulation was possibly lower after immersion in water at 28 and 15°C. No effect of recovery by water immersion was observed for serum levels of creatine kinase and aspartate aminotransferase. Conclusions: Recovery by hot-water immersion likely attenuated the leukocytosis and increased the mobilization of non-classical monocytes induced by a single session of exercise combining resistance and endurance exercises, despite no effect of water immersion on markers of skeletal muscle damage. The monocyte response mediated by hot water immersion may lead to the improvement of the inflammatory response evoked by exercise in the skeletal muscle.

Effects of the association of different volumes of strength training with photobiomodulation therapy on insulin resistance: A protocol for a randomized, triple-blind, placebo-controlled trial.

Background: Insulin resistance (IR) is the main risk factor for developing type 2 diabetes. Both strength training (ST) and photobiomodulation therapy (PBMt) reduce IR, but the effect of combining different volumes of ST with PBMt is unknown. Methods: Overweight/obese individuals will be assigned to 4 groups (n = 12/group): ST with volume following international guidelines (3 sets per exercise - high volume) or one-third of this volume (1 set per exercise - low volume), combined with PBMt or placebo. ST will be performed for 20 sessions over 10 weeks and will consist of 7 exercises. The PBMt will be applied after training sessions using blankets with light emitters (LEDs) placed over the skin on the frontal and the posterior region of the body, following the parameters recommended by the literature. The placebo group will undergo an identical procedure, but blankets will emit insignificant light. To measure plasma glucose and insulin concentrations, oral glucose tolerance tests (OGTT) will be performed before and after the training period. Thereafter, IR, the area under the curve of glucose and insulin, and OGTT-derived indices of insulin sensitivity/resistance will be calculated. Expected impact on the field: This study will determine the effects of different ST volumes on IR and whether the addition of PBMt potentiates the effects of ST. Because previously sedentary, obese, insulin-resistant individuals might not comply with recommended volumes of exercise, the possibility that adding PBMt to low-volume ST enhances ST effects on IR bears practical significance.

Photobiomodulation Therapy on the Treatment of Insulin Resistance: A Narrative Review.

Background: Insulin resistance (IR) is the main risk factor for the development of type 2 diabetes mellitus (DM2). Noninvasive and nonpharmacological therapies, such as exercise and diet are effective in treating IR and DM2; however, adherence to them generally is low and diminishes positive effects in the long term. Photobiomodulation therapy (PBMT) is another noninvasive and nonpharmacological therapy, which produces positive effects on mitochondrial metabolism, oxidative stress, and inflammation generally linked to IR and DM2 and may improve or attenuate the severity of these diseases. Objective: In this narrative review, we focus on the available literature related to the effects of PBMT on IR. Results: In fact, recent in vitro and in vivo studies have demonstrated improvements in IR in skeletal muscle, adipose tissue, and hepatic cells mediated by PBMT. Further, there is evidence that PBMT can potentiate exercise-induced improvement in IR through ameliorating mitochondrial dysfunction, reducing inflammation, and modulating oxidative stress. Moreover, reduced adiposity and altered gut microbiota also appear to mediate PBMT effects on IR. Conclusions: Although these results are exciting, randomized clinical trials are urgently needed to confirm the clinical relevance of PBMT in the treatment of IR. Investigation about the effects of PBMT combined with different volumes of physical exercises may also contribute significantly for those patients having difficulty to adhere to the recommended minimal exercise volume. Finally, studies on PBMT parameters (e.g., dosimetry, wavelengths, single-point vs. full-body irradiation) are also necessary for the appropriate prescription of PBMT for the treatment of IR.

The effect of repetition tempo on cardiovascular and metabolic stress when time under tension is matched during lower body exercise.

PURPOSE: To investigate the effect of repetition tempo on cardiovascular and metabolic stress when time under tension (TUT) and effort are matched during sessions of lower body resistance training (RT). METHODS: In a repeated-measures, cross-over design, 11 recreationally trained females (n = 5) and males (n = 6) performed 5 sets of belt squats under the following conditions: slow-repetition tempo (SLOW; 10 reps with 4-s eccentric and 2-s concentric) and traditional-repetition tempo (TRAD; 20 reps with 2-s eccentric and 1-s concentric). TUT (60 s) was matched between conditions and external load was adjusted so that lifters were close to concentric muscular failure at the end of each set. External load, total volume load (TVL), impulse (IMP), blood lactate, ratings of perceived exertion (RPE), HR, and muscle oxygenation were measured. RESULTS: Data indicated that TVL (p < 0.001), blood lactate (p = 0.017), RPE (p = 0.015), and HR (p < 0.001) were significantly greater during TRAD while external load (p = 0.030) and IMP (p = 0.002) were significantly greater during SLOW. Whether it was expressed as minimal values or change scores, muscle oxygenation was not different between protocols. CONCLUSION: When TUT is matched, TVL, cardiovascular stress, metabolic stress, and perceived exertion are greater when faster repetition tempos are used. In contrast, IMP and external load are greater when slower repetition tempos are used.

The Acute Physiological and Perceptual Responses Between Bodyweight and Treadmill Running High-Intensity Interval Exercises.

Objective: The purpose of this study was to compare the acute physiological, perceptual, and enjoyment responses between bodyweight high-intensity interval exercise (BW-HIIE) and treadmill running high-intensity interval exercise HIIE (RUN-HIIE). Methods: Twelve adults [age: 29.5 ± 5.3 years; weight: 70.9 ± 15.0 kg; height: 167.9 ± 8.9 cm; peak oxygen consumption (VO2 peak): 48.7 ± 6.5 ml min-1·kg-1] performed both RUN-HIIE and BW-HIIE. RUN-HIIE consisted of two sets of 5, 60-s (s) run intervals at 100% of the speed achieved during VO2 peak testing followed by 60s of walking at 4.02 km/h. BW-HIIE consisted of two sets of 5, 60s 'all-out' effort calisthenic exercises followed by 60s of marching in place at 100 steps per minute. Oxygen consumption (VO2), blood lactate (Blac), heart rate (HR), and rating of perceived exertion (RPE) were measured during exercise. Physical activity enjoyment (PACES) was assessed post-exercise. Creatine Kinase (CK) was measured before exercise and 48-h post-exercise. Muscle soreness was assessed before exercise, post-exercise, and 48-h post-exercise. Results: Oxygen consumption relative to VO2 peak was higher (p < 0.001) during RUN-HIIE (88 ± 3%) compared to BW-HIIE (77 ± 4%). HR relative to HRpeak was higher (p = 0.002) for RUN-HIIE (93 ± 1%) compared to BW-HIIE (88 ± 2%). Blac was higher (p < 0.001) after BW-HIIE (11.2 ± 3.2 mmol/l) compared to RUN-HIIE (6.9 ± 2.0 mmol/l). Average RPE achieved was higher (p = 0.003) during BW-HIIE (16 ± 2) than RUN-HIIE (14 ± 2). PACES was similar for RUN-HIIE and BW-HIIE (p > 0.05). No differences (p > 0.05) in CK were observed between RUN-HIIE and BW-HIIE. Conclusion: Our results indicate 'all-out' calisthenic exercise can elicit vigorous cardiorespiratory, Blac, and RPE responses. Implementing this style of exercise into training requires minimal space, no equipment, and may elicit cardiometabolic adaptations seen with traditional forms of high-intensity exercise.

The combined effects of exercise-induced muscle damage and heat stress on acute kidney stress and heat strain during subsequent endurance exercise.

PURPOSE: The purpose of the study was to investigate the combined effect of downhill running and heat stress on muscle damage, as well as on heat strain and kidney stress during subsequent running in the heat. METHODS: In a randomized cross-over study, ten non-heat-acclimated, physically active males completed downhill running in temperate (EIMD in Temp) and hot (EIMD in Hot) conditions followed by an exercise-heat stress (HS) test after 3-h seated rest. Blood and urine samples were collected immediately pre- and post-EIMD and HS, and 24 h post-EIMD (post-24 h). Core temperature and thermal sensation were measured to evaluate heat strain. Serum creatine kinase (CK), maximal voluntary isometric contraction of the quadriceps (MVC) and perceived muscle soreness were measured to evaluate muscle damage. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels were measured to indicate acute kidney stress. RESULTS: CK, MVC and perceived soreness were not different between conditions at any timepoints. In the EIMD in Hot condition, urinary NGAL was significantly elevated from pre- to post-HS (pre-HS: 6.56 {1.53-12.24} ng/min, post-HS: 13.72 {7.67-21.46} ng/min, p = 0.034). Such elevation of NGAL or KIM-1 was not found in the EIMD in Temp condition. CONCLUSIONS: As compared with downhill running in a temperate environment, downhill running in a hot environment does not appear to aggravate muscle damage. However, elevated NGAL levels following EIMD in a hot environment suggest such exercise may increase risk of mild acute kidney injury during subsequent endurance exercise in the heat.

A Real-World High-Intensity Interval Training Protocol for Cardiorespiratory Fitness Improvement.

High-Intensity Interval Training (HIIT) has emerged as an interesting time-efficient approach to increase exercise adherence and improve health. However, few studies have tested the efficiency of HIIT protocols in a "real world" setting, e.g., HIIT protocols designed for outdoor spaces without specialized equipment. This study presents a "real world" training protocol, named "beep training", and compares the efficiency of a HIIT regiment versus a traditional long-duration Moderate-Intensity Continuous Training (MICT) regiment using this beep training protocol on VO2 max of overweight untrained men. Twenty-two subjects performed outdoor running with MICT (n = 11) or HIIT (n = 11). Cardiorespiratory fitness was assessed before and after training protocols using a metabolic analyzer. Both training protocols were performed 3 days a week for 8 weeks using the Beep Test results. The MICT group performed the exercise program at 60%-75% of the maximum speed of the 20 m shuttle test (Vmax) and with a progression of the distance of 3,500-5,000 m. The HIIT group performed the interval exercise with 7-10 bouts of 200 m at 85%-100% of the maximum speed of the 20 m shuttle test (Vmax), interspersed with 1 min of passive recovery. Although the HIIT group presented a significantly lower training volume than the MICT group (p < 0.05) after 8 weeks of beep training, HIIT was superior to MICT in improving VO2 max (MICT: ~4.1%; HIIT: ~7.3%; p < 0.05). The "real world" HIIT regiment based on beep training protocol is a time-efficient, low-cost, and easy-to-implement protocol for overweight untrained men.

Accumulated High-intensity Interval Training Protocol: A New Approach to Study Health Markers in Wistar Rats.

High-Intensity Interval Training (HIIT) and accumulated exercises are two time-efficient programs to improve health in humans and animal models. However, to date, there are no studies on whether HIIT performed in an accumulated fashion is as effective as a traditional HIIT performed with single daily sessions in improving health markers. This paper presents the effects of a new HIIT protocol, called accumulated HIIT, on body weight gain, maximal oxygen consumption (VO2max), and cardiac hypertrophy in young Wistar rats. Sixty-day-old male Wistar rats were assigned to three groups: untrained (UN; n = 16), HIIT performed with single daily sessions (1-HIIT; n = 16), and HIIT performed with three daily sessions (3-HIIT; n = 16). Body weight and VO2max were recorded before and after the training period. The VO2max measurements were taken using a metabolic analyzer at the maximal running velocity (Vmax). The training was performed for both HIIT groups five days per week over eight weeks with the same weekly progression of the exercise intensity (85-100% Vmax). The 1-HIIT group performed single daily sessions (6 bouts of 1 min interspersed with 1 min of passive recovery). The 3-HIIT group performed three daily sessions (2 bouts of 1 min interspersed with 1 min of passive recovery with an interval of 4 h between bouts). After the last VO2max test, the rats were euthanized, and their hearts were harvested and weighed. The results showed that 3-HIIT had similar beneficial effects to 1-HIIT in preventing body weight gain, improving VO2max, and inducing cardiac hypertrophy. These findings reveal for the first time the efficacy of an accumulated HIIT protocol on the health markers of young Wistar rats. This new HIIT protocol may be more feasible than traditional HIIT protocols as exercise can be split into very short sessions throughout a day in this new approach.

Repeated sprint exercise in hypoxia stimulates HIF-1-dependent gene expression in skeletal muscle.

PURPOSE: Our aim was to determine the effect of repeated sprint exercise in hypoxia on HIF-1 and HIF-1-regulated genes involved in glycolysis, mitochondrial turnover and oxygen transport. We also determined whether genes upregulated by exercise in hypoxia were dependent on the activation of HIF-1 in an in vitro model of exercise in hypoxia. METHODS: Eight endurance athletes performed bouts of repeated sprint exercise in control and hypoxic conditions. Skeletal muscle was sampled pre, post and 3 h post-exercise. HIF-1α protein and HIF1A, PDK1, GLUT4, VEGFA, BNIP3, PINK1 and PGC1A mRNA were measured. C2C12 myotubes were exposed to hypoxia and muscle contraction following treatment with a HIF-1α inhibitor to determine whether hypoxia-sensitive gene expression was dependent on HIF-1α. RESULTS: Sprint exercise in hypoxia increased HIF-1α protein expression immediately post-exercise [fold change (FC) = 3.5 ± 2.0]. Gene expression of PDK1 (FC = 2.1 ± 1.2), BNIP3 (FC = 2.4 ± 1.4) and VEGFA (FC = 2.7 ± 1.7) increased 3 h post-exercise in hypoxia but not control. PGC1A mRNA increased 3 h post-exercise in control (FC = 5.16) and hypoxia (FC = 5.7 ± 4.1) but there was no difference between the trials. Results from the in vitro experiment showed that hypoxia plus contraction also increased PDK1, BNIP3, and VEGFA gene expression. These responses were inhibited when HIF-1 protein activity was suppressed. CONCLUSION: Repeated sprint exercise in hypoxia upregulates some genes involved in glycolytic metabolism, mitochondrial turnover, and oxygen transport. HIF-1α is necessary for the expression of these genes in skeletal muscle cells.

Aerobic Adaptations to Resistance Training: The Role of Time under Tension.

Generally, skeletal muscle adaptations to exercise are perceived through a dichotomous lens where the metabolic stress imposed by aerobic training leads to increased mitochondrial adaptations while the mechanical tension from resistance training leads to myofibrillar adaptations. However, there is emerging evidence for cross over between modalities where aerobic training stimulates traditional adaptations to resistance training (e.g., hypertrophy) and resistance training stimulates traditional adaptations to aerobic training (e.g., mitochondrial biogenesis). The latter is the focus of the current review in which we propose high-volume resistance training (i.e., high time under tension) leads to aerobic adaptations such as angiogenesis, mitochondrial biogenesis, and increased oxidative capacity. As time under tension increases, skeletal muscle energy turnover, metabolic stress, and ischemia also increase, which act as signals to activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha, which is the master regulator of mitochondrial biogenesis. For practical application, the acute stress and chronic adaptations to three specific forms of high-time under tension are also discussed: Slow-tempo, low-intensity resistance training, and drop-set resistance training. These modalities of high-time under tension lead to hallmark adaptations to resistance training such as muscle endurance, hypertrophy, and strength, but little is known about their effect on traditional aerobic training adaptations.

High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity.

One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; ∼200%, P=0.0008), early erythroid progenitor colonies (∼300%, P<0.0001) and reticulocytes (∼500%, P=0.0007), and reduced erythrocyte lifespan (∼50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg-1.day-1). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.

Strength training improves insulin resistance and differently affects mitochondria in skeletal muscle and visceral adipose tissue in high-fat fed mice.

AIMS: Strength training (ST) improves insulin resistance and glucose tolerance by yet unknown mechanisms. The aims of this study were to investigate the effects of ST on mitochondrial adaptation in skeletal muscle and adipose tissue, on heat shock protein 72 (Hsp72) in skeletal muscle, and on visceral adipocyte size in mice with high-fat diet (HFD)-induced insulin resistance. MATERIALS AND METHODS: Male Balb/c mice were divided into sedentary control-chow (C-chow), strength trained-chow (ST-chow), sedentary control-HFD (C-HFD) and strength trained-HFD (ST-HFD). Diet was provided for 12 weeks, while ladder climbing ST was performed for the final six weeks of the study at a frequency of three days per week. KEY FINDINGS: Strength training led to increased strength, muscular endurance, and skeletal muscle hypertrophy. Compared to the C-HFD group, mice in the ST-HFD group decreased their whole-body insulin resistance, improved their glucose tolerance, and had higher activation of the insulin pathway in skeletal muscle. ST increased citrate synthase (CS) activity in skeletal muscle, but this increase was blunted in ST-HFD. Conversely, HFD reduced adipose tissue CS activity regardless of training status. Hsp72 content was reduced in C-HFD, but returned to control levels in ST-HFD. Finally, reduced epididymal adipocyte size was observed in ST-HFD. SIGNIFICANCE: These results suggest that the improvement in insulin resistance induced by ST is related to mitochondrial adaptation in skeletal muscle, but not in adipose tissue. Moreover, this improvement might be related to increased skeletal muscle Hsp72 and reduced epididymal adipocyte size.