Small peptides: could they have a big role in metabolism and the response to exercise?

Exercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mechanisms responsible for the many beneficial adaptations to exercise. This has led to increased research into the role of small peptides (<100 amino acids) and mitochondrially derived peptides in metabolism and disease, including those coded within small open reading frames (sORFs; coding sequences that encode small peptides). Recently, it has been hypothesized that sORF-encoded mitochondrially derived peptides and other small peptides play significant roles as exercise-sensitive peptides in exercise-induced physiological adaptation. In this review, we highlight the discovery of mitochondrially derived peptides and newly discovered small peptides involved in metabolism, with a specific emphasis on their functions in exercise-induced adaptations and the prevention of metabolic diseases. In light of the few studies available, we also present data on how both single exercise sessions and exercise training affect expression of sORF-encoded mitochondrially derived peptides. Finally, we outline numerous research questions that await investigation regarding the roles of mitochondrially derived peptides in metabolism and prevention of various diseases, in addition to their roles in exercise-induced physiological adaptations, for future studies.

Reallocating just 10 min to moderate-to-vigorous physical activity from other components of 24-hour movement behaviors improves cardiovascular health in adults.

BACKGROUND: As components of a 24-hour day, sedentary behavior (SB), physical activity (PA), and sleep are all independently linked to cardiovascular health (CVH). However, insufficient understanding of components' mutual exclusion limits the exploration of the associations between all movement behaviors and health outcomes. The aim of this study was to employ compositional data analysis (CoDA) approach to investigate the associations between 24-hour movement behaviors and overall CVH. METHODS: Data from 581 participants, including 230 women, were collected from the 2005-2006 wave of the US National Health and Nutrition Examination Survey (NHANES). This dataset included information on the duration of SB and PA, derived from ActiGraph accelerometers, as well as self-reported sleep duration. The assessment of CVH was conducted in accordance with the criteria outlined in Life's Simple 7, encompassing the evaluation of both health behaviors and health factors. Compositional linear regression was utilized to examine the cross-sectional associations of 24-hour movement behaviors and each component with CVH score. Furthermore, the study predicted the potential differences in CVH score that would occur by reallocating 10 to 60 min among different movement behaviors. RESULTS: A significant association was observed between 24-hour movement behaviors and overall CVH (p < 0.001) after adjusting for potential confounders. Substituting moderate-to-vigorous physical activity (MVPA) for other components was strongly associated with favorable differences in CVH score (p < 0.05), whether in one-for-one reallocations or one-for-remaining reallocations. Allocating time away from MVPA consistently resulted in larger negative differences in CVH score (p < 0.05). For instance, replacing 10 min of light physical activity (LPA) with MVPA was related to an increase of 0.21 in CVH score (95% confidence interval (95% CI) 0.11 to 0.31). Conversely, when the same duration of MVPA was replaced with LPA, CVH score decreased by 0.67 (95% CI -0.99 to -0.35). No such significance was discovered for all duration reallocations involving only LPA, SB, and sleep (p > 0.05). CONCLUSIONS: MVPA seems to be as a pivotal determinant for enhancing CVH among general adult population, relative to other movement behaviors. Consequently, optimization of MVPA duration is an essential element in promoting overall health and well-being.

Effect of Pre-exercise Sodium Citrate Ingestion on Repeated Sprint Performance in Soccer Players.

ABSTRACT: Kuru, D, Aktitiz, S, Atakan, MM, Köse, MG, Turnagöl, HH, and Kosar, SN. Effect of pre-exercise sodium citrate ingestion on repeated sprint performance in soccer players. J Strength Cond Res 38(3): 556-562, 2024-This study aimed to test the hypothesis that sodium citrate (CIT) administered 180 minutes before exercise improves repeated sprint performance in athletes within a field-based setting. Twenty male soccer players (mean ± SD : age = 20.9 ± 2.3 years; body mass [BM] = 73.8 ± 5.9 kg) performed a running-based anaerobic sprint test (RAST) with 0.5 g·kg -1 BM of CIT or with placebo (PLC; NaCl) ingestion 180 minutes before exercise in a randomized, crossover, and double-blind design, with at least 6 days between the trials. Blood samples were collected before exercise and at first, third, fifth, and seventh minutes after exercise to analyze blood pH, bicarbonate, and lactate levels. Gastrointestinal symptoms were also monitored at 30-minute intervals for 180 minutes after CIT and PLC ingestion. Pre-exercise blood pH (CIT = 7.49 ± 0.03 vs. PLC = 7.41 ± 0.02) and bicarbonate (CIT = 30.57 ± 1.33 vs. PLC = 25.25 ± 1.52) increased with CIT compared with PLC ( p < 0.001). Blood pH, bicarbonate, and lactate at the first, third, fifth, and seventh minutes after RAST with CIT were higher than PLC ( p < 0.05), except for lactate at first minute ( p > 0.05). Compared with PLC, CIT ingestion significantly improved minimum power output ( p = 0.024) and percentage decrement score ( p = 0.023). Gastrointestinal symptoms were significantly higher after CIT ingestion vs. PLC at 30th ( p = 0.003) and 60th minutes ( p = 0.010). However, there were no significant differences at 90th, 120th, 150th, or 180th minutes ( p > 0.05). The ingestion of 0.5 g·kg -1 BM of CIT 180 minutes before exercise is an effective ergogenic aid for improving repeated sprint ability as evidenced by improvements in minimum power output and percentage decrement score.

Effects of high-intensity interval training (HIIT) and sprint interval training (SIT) on fat oxidation during exercise: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of high-intensity interval training (HIIT) and sprint interval training (SIT) on fat oxidation during exercise (FatOx) and how they compare with the effects of moderate-intensity continuous training (MICT). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Academic Search Ultimate, CINAHL, Networked Digital Library of Theses and Dissertations, Open Access Theses and Dissertations, OpenDissertations, PubMed/MEDLINE, Scopus, SPORTDiscus and Web of Science. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies using a between-group design, involving adult participants who were not trained athletes, and evaluating effects of HIIT or SIT on FatOx (vs no exercise or MICT) were included. RESULTS: Eighteen studies of fair-to-good quality were included; nine comparing HIIT or SIT with no exercise and eleven comparing HIIT or SIT with MICT. A significant pooled effect of these types of interval training on FatOx was found (mean difference in g/min (MD)=0.08; 95% confidence interval (CI) 0.04 to 0.12; p<0.001). Significant effects were found for exercise regimens lasting ≥4 weeks, and they increased with every additional week of training (ß=0.01; 95% CI 0.00 to 0.02; p=0.003). HIIT and/or SIT were slightly more effective than MICT (MD=0.03; 95% CI 0.01 to 0.05; p=0.005). The effects on FatOx were larger among individuals with overweight/obesity. CONCLUSION: Engaging in HIIT or SIT can improve FatOx, with larger effects expected for longer training regimens and individuals with overweight/obesity. While some effects seem small, they may be important in holistic approaches to enhance metabolic health and manage obesity.

Methods to match high-intensity interval exercise intensity in hypoxia and normoxia - A pilot study.

The aim of this study was to compare high-intensity interval exercise (HIIE) sessions prescribed on the basis of a maximal value (peak power output, PPO) and a submaximal value (lactate threshold, LT) derived from graded exercise tests (GXTs) in normoxia and hypoxia. METHODS: A total of ten males (aged 18-37) volunteered to participate in this study. The experimental protocol consisted of a familiarization procedure, two GXTs under normoxia (FiO2 = 0.209) and two GXTs under normobaric hypoxia (FiO2 = 0.140), and three HIIE sessions performed in a random order. The HIIE sessions included one at hypoxia (HY) and two at normoxia (one matched for the absolute intensity in hypoxia, designated as NA, and one matched for the relative intensity in hypoxia, designated as NR). RESULTS: The data demonstrated that there was significant lower peak oxygen uptake (V̇O2peak), peak heart rate (HRpeak), PPO, and LT derived from GXTs in hypoxia, with higher respiratory exchange ratio (RER), when compared to those from GXTs performed in normoxia (p < 0.001). Among the three HIIE sessions, the NA session resulted in lower percentage of HRpeak (85.0 ± 7.5% vs 94.4 ± 5.0%; p = 0.002) and V̇O2peak (74.1 ± 9.1% vs 88.7 ± 7.7%; p = 0.005), when compared to the NR session. HIIE sessions in HY and NR resulted in similar percentage of HRpeak and V̇O2peak, as well as similar rating of perceived exertion and RER. The blood lactate level increased immediately after all the three HIIE sessions (p < 0.001), while higher blood lactate concentrations were observed immediately after the HY (p = 0.0003) and NR (p = 0.014) sessions when compared with NA. CONCLUSION: Combining of PPO and LT derived from GXTs can be used to prescribe exercise intensity of HIIE in hypoxia.

Ten weeks of low-volume walking training improve cardiometabolic health and body composition in sedentary postmenopausal women with obesity without affecting markers of bone metabolism.

This study aimed to determine the effects of walking exercise to induce a mild energy deficit and to improve body composition and metabolic status in postmenopausal women (PMW) with obesity as means of minimizing endocrine disruption and maintaining bone health. Twenty-four PMW with obesity (age: 55.0 ± 3.7 y, BMI: 32.9 ± 4.2 kg/m2, percent body fat: 46.2 ± 3.6%) were randomly assigned into either exercise (n = 12) or control (n = 12) groups. Exercise group participated in a-10 week supervised progressive walking programme and control group maintained regular habits. Pre- and post-training assessments included body composition, bone mass, peak oxygen uptake (V˙O2peak), osteocalcin, bone alkaline phosphatase (BAP), type I collagen cross-linked C-telopeptide (CTX)glucose, glycated haemoglobin (HbA1c)), leptin and adiponectin. Results: Following the training program, body weight (2.6%; p < 0.001), fat mass (4.5%; p = 0.002), resting glucose (6.8%; p = 0.017), and HbA1c (3.7%; p = 0.047) decreased, while relative V˙O2peak (16%; p < 0.001) increased in the exercise group. Leptin, adiponectin, CTX, osteocalcin or BAP did not change in either group. In conclusion, small dose of aerobic exercise improves key markers of metabolic health in PMW with obesity without negatively affecting markers of bone metabolism.

Acute Pilates and plyometric exercise in school-based settings improve attention and mathematics performance in high school students.

The aim of this study was to examine the effects of acute Pilates and plyometric exercise in a school-based setting on attention and mathematics test performance in high school students. Forty 10th-grade students (21 females and 19 males; age: [15.0 ± 0.5] years, body mass index: [21.4 ± 2.8] kg/m2) participated in this crossover and quasi-experimental study. In week 1, students were familiarized with the d2 test of attention and Pilates and plyometric exercises activities, and body composition measurements were taken. In both weeks 2 and 3, students completed the d2 test of attention and mathematics test with 20 questions following a single session of low-to-moderate-intensity exercise and a classroom-based non-exercise activity, in a non-randomized order. The exercise sessions included 30 mins of plyometric exercises for male students and Pilates exercise for female students, with intensities corresponding to 10-14 on the Borg rating of perceived exertion scale6-20. Compared to the non-exercise activity, a 30-min of Pilates and plyometric exercise resulted in significant improvements in attention score (mean difference [Δ] â€‹= â€‹54.5 score; p â€‹< 0.001; Cohen's effect sizes [d] â€‹= â€‹1.26) and concentration performance (Δ â€‹= â€‹20.7 score; p â€‹= â€‹0.003; d â€‹= â€‹0.51). The students scored significantly higher on the mathematics test after participating in the exercise sessions compared to the non-exercise condition (Δ% â€‹= â€‹11.7; p â€‹< â€‹0.001; d â€‹= â€‹0.76). There were no significant differences between genders (p â€‹> â€‹0.05). These findings demonstrate the effectiveness of acute light-to-moderate-intensity Pilates and plyometric exercises in school-based settings for improving attention and mathematics performance in adolescents.

Progressive Arm Cycling Ergometry With 3- And 5-Minute Stage Durations Yields Similar Estimates of Substrate Oxidation in Healthy Adults.

Arm cycling ergometry (ACE) leads to a lower maximal oxygen uptake (VO2max) than cycling which is related to a smaller active muscle mass. This study compared estimates of fat and carbohydrate oxidation (FOx and CHOOx) between progressive exercise protocols varying in stage duration in an attempt to create a standard exercise protocol for determining substrate metabolism using ACE. Four men and seven women (age = 24 ± 9 yr) unfamiliar with ACE completed incremental exercise to determine peak power output and VO2peak. During two subsequent sessions completed after an overnight fast, they completed progressive ACE using 3- or 5-min stages during which FOx, CHOOx, and blood lactate concentration (BLa) were measured. Results showed no difference (p > 0.05) in FOx, CHOOx, or BLa across stage duration, and there was no difference in maximal fat oxidation (0.16 ± 0.08 vs. 0.13 ± 0.07 g/min, p = 0.07). However, respiratory exchange ratio in response to the 3 min stage duration was significantly lower than the 5 min duration (0.83 ± 0.05 vs. 0.86 ± 0.03, p = 0.04, Cohen's d = 0.76). Results suggest that a 3 min stage duration is preferred to assess substrate metabolism during upper-body exercise in healthy adults.

Effects of 4-Week Low-Load Resistance Training with Blood Flow Restriction on Muscle Strength and Left Ventricular Function in Young Swimmers: A Pilot Randomized Trial.

Low-load resistance training combined with blood flow restriction (BFR) is known to result in muscle hypertrophy and strength similar to that observed with higher loads. However, the effects of resistance training with BFR on cardiac structure and cardiac function remain largely unknown. Therefore, the purpose of this randomized study was to compare the effects of conventional high-load resistance training (HL-RT) with the effects of low-load resistance training with BFR (LL-BFR) on muscle strength and left ventricular function. Sixteen young swimmers (mean ± standard deviation: age = 19.7 ± 1.6 years, body mass = 78.9 ± 9.7 kg, body height = 180.8 ± 5.8 cm) were randomly allocated to a conventional HL-RT group (n = 8) or a LL-BFR group (n = 8) with a pressure band (200 mmHg) placed on both thighs of participants for 4 weeks (3 days•week-1). Outcome measures were taken at baseline and after 4 weeks of training, and included body composition, one-repetition maximum (1RM) back squat, and echocardiography measures. The 1RM back squat significantly improved (partial eta squared (È 2) = 0.365; p = 0.013) in HL-RT (mean difference (Δ) = 6.6 kg; [95% confidence interval (CI) -7.09 to 20.27]) and LL-BFR groups (Δ = 14.7 kg; [95% CI 3.39 to 26.10]), with no main effect of group or group × time interaction (p > 0.05). Interventricular septum end-systolic thickness showed a slight but statistically significant increase in LL-BFR and HL-RT groups (È 2 = 0.253; p = 0.047), yet there was no main effect of group or group × time interaction (p > 0.05). There were no statistically significant changes (p > 0.05) in other cardiac structure or function parameters (e.g., left ventricular (LV) mass, LV cardiac output, LV ejection fraction, LV stroke volume) after the training programs. Results suggest that 4 weeks of HL-RT and LL-BFR improve muscle strength similarly with limited effects on left ventricular function in young swimmers.

Interleukin-6, undercarboxylated osteocalcin, and brain-derived neurotrophic factor responses to single and repeated sessions of high-intensity interval exercise.

OBJECTIVES: The purpose of this study was to compare the effects of a single session of high-intensity interval exercise (HIIE) with 2 consecutive HIIEs, separated by 3 h of recovery, on plasma interleukin-6 (IL-6), undercarboxylated osteocalcin (ucOC), and brain-derived neurotrophic factor (BDNF) responses. METHODS: Twenty male recreational endurance athletes completed two HIIE trials in a randomized crossover design: a single session of HIIE on the single exercise day (HIIE-S) and two sessions of HIIE 3 h apart on the double exercise day (HIIE-D). The HIIE protocol consisted of 10 × 1 min cycling at 100 % of peak oxygen uptake, with 75 s of low-intensity cycling at 60 W. Blood samples were collected to analyze IL-6, ucOC, and BDNF levels before and immediately after HIIE on the HIIE-S and before and immediately after the second HIIE on the HIIE-D. RESULTS: Both HIIE interventions significantly increased (p < 0.001) plasma IL-6 (HIIE-S 33.90 % vs HIIE-D 31.04 %; p = 0.64), ucOC (HIIE-S 37.18 % vs HIIE-D 39.54 %; p = 0.85), and BDNF levels (HIIE-S 236.01 % vs HIIE-D 216.68 %; p = 0.69), with no group effect. CONCLUSIONS: Our results demonstrate that performing two consecutive HIIEs on the same day with a 3-h rest results in similar changes in plasma levels of IL-6, BDNF, and ucOC compared with a single session of HIIE.

Exercise and Metabolic Health: The Emerging Roles of Novel Exerkines.

Physical inactivity is a major cause of chronic diseases. It shortens the health span by lowering the age of the first chronic disease onset, which leads to decreased quality of life and increased mortality risk. On the other hand, physical exercise is considered a miracle cure in the primary prevention of at least 35 chronic diseases, including obesity, insulin resistance, and type 2 diabetes. However, despite many scientific attempts to unveil the health benefits conferred by regular exercise, the underlying molecular mechanisms driving such benefits are not fully explored. Recent research shows that exercise-induced bioactive molecules, named exerkines, might play a critical role in the regulation of metabolic homeostasis and thus prevent metabolic diseases. Here we summarize the current understanding of the health-promoting effects of exerkines secreted from skeletal muscle, adipose tissue, bone, and liver, including MOTS-c, BDNF, miR-1, 12,13-diHOME, irisin, SPX, OC, GDF15, and FGF21 on obesity, insulin resistance, and type 2 diabetes. Identifying the systemic health benefits of exerkines may open a new area for the discovery of new pharmacological strategies for the prevention and management of metabolic diseases.

Graded exercise test with or without load carriage similarly measures maximal oxygen uptake in young males and females.

The aim of this was to compare the effects of the graded exercise test (GXT) with or without load carriage on maximal oxygen uptake ([Formula: see text]) heart rate (HR), and expired ventilation ([Formula: see text]) and blood lactate in young healthy males and females. The study included ten females (age:20.2±0.7 yrs) and ten males (age:19.5±0.7 yrs) who performed the modified Bruce protocol at five load conditions; unloaded, 5, 10, 15, and 20% of body weight (BW) (kg). All the tests were performed in random order, at least 48 hours apart. During the GXTs, HR, [Formula: see text], [Formula: see text], workload and test duration were recorded and blood lactate concentration was measured before and immediately after the GXTs. [Formula: see text] remained unchanged during the GXTs in load and unloaded conditions for both sexes (p>0.05). Test duration was significantly less in females during the GXT with 15% BW (15.9±0.51 min vs. 18.1±1.14 min; p = 0.014) and 20% BW load carriage (15.2±0.75 min vs. 18.1±1.14 min; p = 0.020), compared to the unloaded GXT. Males showed significant decrease in the test duration during the GXT with load 15% BW (20.5±0.53 min vs. 22.8±0.61 min; p = 0.047) and with 20% BW (19.6±0.42 min vs. 22.8±0.71 min; p = 0.004), compared to the GXT with 5% BW. [Formula: see text] statistically decreased in female subjects only at 15% BW compared to 20% BW (15% BW = 77.9 ± 10.5 L/min vs. 15% BW = 72.0 ± 10.9 L/min; p = 0.045). There was no difference observed in maximal HR and blood lactate concentration between the GXTs in load and unloaded conditions. This study indicates that no matter the load % used during the GXT, [Formula: see text], but not total exercise time, remains the same in young males and females.

Six high-intensity interval training sessions over 5 days increases maximal oxygen uptake, endurance capacity, and sub-maximal exercise fat oxidation as much as 6 high-intensity interval training sessions over 2 weeks.

BACKGROUND: High-intensity interval training (HIIT) induces similar or even superior adaptations compared to continuous endurance training. Indeed, just 6 HIIT sessions over 2 weeks significantly improves maximal oxygen uptake (VO2max), submaximal exercise fat oxidation, and endurance performance. Whether even faster adaptations can be achieved with HIIT is not known. Thus, we aimed to determine whether 2 sessions of HIIT per day, separated by 3 h, every other day for 5 days (double HIIT (HIIT-D), n = 15) could increase VO2max, submaximal exercise fat oxidation, and endurance capacity as effectively as 6 sessions of HIIT over 2 weeks (single HIIT (HIIT-S), n = 13). METHODS: Each training session consisted of 10 × 60 s of cycling at 100% of VO2max interspersed with 75 s of low-intensity cycling at 60 watt (W). Pre- and post-training assessments included VO2max, time to exhaustion at ∼80% of VO2max, and 60-min cycling trials at ∼67% of VO2max. RESULTS: Similar increases (p < 0.05) in VO2max (HIIT-D: 7.7% vs. HIIT-S: 6.0%, p > 0.05) and endurance capacity (HIIT-D: 80.1% vs. HIIT-S: 79.2%, p > 0.05) were observed. Submaximal exercise carbohydrate oxidation was reduced in the 2 groups after exercise training (HIIT-D: 9.2%, p = 0.014 vs. HIIT-S: 18.8%, p = 0.012) while submaximal exercise fat oxidation was significantly increased in HIIT-D (15.5%, p = 0.048) but not in HIIT-S (9.3%, p = 0.290). CONCLUSION: Six HIIT sessions over 5 days was as effective in increasing VO2max and endurance capacity and was more effective in improving submaximal exercise fat oxidation than 6 HIIT sessions over 2 weeks.

The Molecular Adaptive Responses of Skeletal Muscle to High-Intensity Exercise/Training and Hypoxia.

High-intensity exercise/training, especially interval exercise/training, has gained popularity in recent years. Hypoxic training was introduced to elite athletes half a century ago and has recently been adopted by the general public. In the current review, we have summarised the molecular adaptive responses of skeletal muscle to high-intensity exercise/training, focusing on mitochondrial biogenesis, angiogenesis, and muscle fibre composition. The literature suggests that (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) PGC-1α, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1-alpha (HIF1-α) might be the main mediators of skeletal muscle adaptations to high-intensity exercises in hypoxia. Exercise is known to be anti-inflammatory, while the effects of hypoxia on inflammatory signalling are more complex. The anti-inflammatory effects of a single session of exercise might result from the release of anti-inflammatory myokines and other cytokines, as well as the downregulation of Toll-like receptor signalling, while training-induced anti-inflammatory effects may be due to reductions in abdominal and visceral fat (which are main sources of pro-inflammatory cytokines). Hypoxia can lead to inflammation, and inflammation can result in tissue hypoxia. However, the hypoxic factor HIF1-α is essential for preventing excessive inflammation. Disease-induced hypoxia is related to an upregulation of inflammatory signalling, but the effects of exercise-induced hypoxia on inflammation are less conclusive. The effects of high-intensity exercise under hypoxia on skeletal muscle molecular adaptations and inflammatory signalling have not been fully explored and are worth investigating in future studies. Understanding these effects will lead to a more comprehensive scientific basis for maximising the benefits of high-intensity exercise.