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.

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.

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.

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.

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.