Original Research
Frontiers in Adolescent Medicine ·
Volume 4 - 2026 | https://doi.org/10.3389/fradm.2026.1742863
Effects of continuous and interval training on brain-derived neurotrophic factor concentrations and executive function in physically inactive adolescents with overweight and obesity
- Francisco José de Menezes-Junior1
- Caroline Brand2
- Maiara Cristina Tadiotto1*corresponding author
- Tatiana Aparecida Affornali Tozo1
- Patricia Ribeiro Paes Corazza1
- Jorge Mota3
- Beatriz Pereira4
- Rafaela Rosário5,6
- Neiva Leite1,3,4
- 1Research Nucleus on the Quality of Life, NQV, Federal University of Paraná, Curitiba, Brazil
- 2IRys Group, Physical Education School, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
- 3Research Centre for Physical Activity, Health and Leisure, CIAFEL, University of Porto, Porto, Portugal
- 4Research Centre on Child Studies, CIEC, University of Minho, Braga, Portugal
- 5School of Nursing, University of Minho, Braga, Portugal
- 6Health Sciences Research Unit: Nursing (UICISA: E), Nursing School of Coimbra, Coimbra, Portugal
Abstract
This study aimed to analyze the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the plasma concentrations of brain-derived neurotrophic factor (BDNF) and executive function in physically inactive adolescents with overweight and obesity. Fiftythree participants (14.01 ± 2.09 years, 27 girls and 26 boys) were allocated to a HIIT program (n = 15), MICT (n = 14) or a control group (CG; n = 24). Exercise sessions were conducted on stationary bikes three times a week for 12 weeks. The MICT session lasted 60 min and the HIIT session lasted approximately 35 min. The variables included plasma BDNF concentrations and measures of executive function, specifically cognitive flexibility and inhibitory control, assessed using the Trial-Making Test and Stroop Test. There was a significant increase in BDNF level for HIIT (Δ = 70.43 pg/mL, p = 0.003), but not for MICT (Δ = 21.17 pg/mL, p = 0.391) and CG (Δ = −3.09 pg/mL, p = 0.865). Thus, we observed a significant improvement in cognitive flexibility for HIIT group (Δ = −59.62″, p < 0.001), but not in the MICT (Δ = −9.32″; p = 0.806) and CG (Δ = 3.15″; p = 0.834). For inhibitory control, there was a significant improvement in both HIIT (Δ = −39.88″, p < 0.001) and MICT (Δ = −31.55″, p = 0.001). In conclusion, both MICT and HIIT programs can benefit the cognitive function in physical inactive adolescents with overweight and obesity. We observed a significant increase in BDNF only in HIIT training,while MICT did not show significant changes compared to the CG.
Keywords
Highlights
- Significant improvement in cognitive flexibility was observed in the HIIT group, while both the HIIT and MICT groups demonstrated significant improvements in inhibitory control;
- High-intensity interval training induces a moderate to large increase in resting plasma BDNF levels compared to control group;
- Changes in plasma BDNF levels appear to be dependent on exercise intensity.
1 Introduction
The prevalence of obesity among children and adolescents has increased substantially over recent decades, rising from 1.7% to 6.9% in girls and from 2.1% to 9.3% in boys between 1990 and 2022 (1). Specifically, obesity among adolescents aged 10–19 years, has more than tripled worldwide (2), and has been associated with alterations in brain structure and deficits in executive function (3). In this context, physical exercise has emerged not only as a strategy for managing obesity, but also as a means to enhance cognitive development and academic performance in children and adolescents (4). A hypothetical mechanism for these cognitive benefits is that exercise increases brain-derived neurotrophic factor levels (BDNF) (5). BDNF is a protein of the neurotrophic family produced by both the brain and skeletal muscles (6). It plays a pivotal role in the growth, differentiation, and survival of neurons (7). These functions are collectively crucial for learning and memory processes, which in turn are essential for enhancing academic performance and overall brain health (8).
Despite growing interest in the relationship between physical exercise and neurotrophic factors, a notable gap remains regarding the effects of different exercise modalities and intensities on BDNF concentrations. There is consistent evidence that sustained moderate-intensity continuous training (MICT) increases circulating BDNF in adults (9) and youth (10). A systematic review with meta-analysis showed that studies with MICT intervention demonstrated increased serum BDNF concentrations after 8-24 weeks of aerobic training in adolescents (10). On the other hand, Although high-intensity interval training (HIIT) has been widely recognized for its cardiometabolic benefits (11), findings on its chronic effects on BDNF remain inconsistent. Some studies have reported significant increases in circulating BDNF levels following prolonged HIIT interventions in adults, particularly when programs lasted 8–12 weeks and were performed consistently (12, 13). However, other studies found no significant changes, or even reductions, in resting BDNF concentrations after chronic HIIT (14, 15). In adolescents, the evidence is still emerging, but a few studies suggest that HIIT may also promote increases in BDNF and cognitive function in this population, although less is knows about its effects on adolescents with overweight/obesity. A systematic review indicated that aerobic exercise protocols,including those with high intensity, appear to be promising strategies to stimulate BDNF secretion in adolescents, although the magnitude and consistency of these effects remain unclear and require further investigation (16).
In addition, given that HIIT involves lower training volume while providing similar or even superior cardiometabolic and physical fitness benefits to MICT (11), it has been proposed as an efficient alternative to enhance cognitive performance in adolescents (4). Supporting this, a recent systematic review analyzed the effects of acute and chronic HIIT interventions on executive function domains in 352 children and adolescents. The review identified a positive effect of acute HIIT on inhibitory control and beneficial effects of chronic HIIT on both inhibitory control and working memory (4). However, it is important to note that most of the available evidence is based on studies involving non-obese children and adolescents, highlighting the need for research in populations with overweight or obesity.
Given the current gaps in the literature and the fact that adolescence is a critical period for brain development, particularly in the prefrontal cortical regions responsible for executive functions (17), it is essential to identify strategies that support brain health during this stage. Enhancing neurocognitive development at this time may positively influence academic performance and long-term professional outcomes. Therefore, the present study aimed to compare the effects of MICT and HIIT on plasma BDNF concentrations and executive function in physically inactive adolescents with overweight and obesity.
2 Methods
2.1 Study design
An experimental study was carried out with adolescents from a city in southern Brazil. The selection of participants and data collection was carried out in 2019 and all participants and guardians signed an informed consent form before the initial assessments. This study was approved by the Ethics Committee of Centro Universitário UniDomBosco (CAAE:62963916.0.0000.5223) and registered in the Brazilian Registry of Clinical Trials (protocol: RBR-6343y7). The sample size was calculated a priori using the G*Power software (v. 3.1.9.2), through the mixed ANOVA with repeated measures, with 2 measures and 3 groups. A power of 0.95, α of 0.05, and effect size (f) of 0.30 were assigned. Based on these criteria, the minimum sample size was 13 participants for each group.
2.2 Participants
The selection of participants and data collection involved adolescents from a city in southern Brazil. The adolescents were recruited through a non-probabilistic sampling process, for convenience. All participants and guardians signed an informed consent form before the initial assessments, and underwent medical evaluations, which included clinical assessments by a pediatrician. Of the 72 volunteer adolescents, 53 met the eligibility criteria and were allocated to one of three groups for 12 weeks: MICT (n = 14; 4 boys and 9 girls), HIIT (n = 15; 9 boys and 4 girls), or control group (CG, n = 24; 13 boys and 11 girls). All participants were between 10 and 17 years old, with 20 adolescents aged 10–13 and 33 adolescents aged 14–17. Adolescents diagnosed with overweight and obesity were selected based on the body mass index (BMI ≥ 85th percentile for age and sex); of both sexes; aged between 10 and 17 years; who did not present medical contraindications to the proposed evaluations, including the absence of cardiac, pulmonary and osteoarticular diseases that could compromise the proposed activities; physically inactive in the previous 6 months, except school physical education; who do not use any medication that interferes with the research results; and that they did not present any cognitive incapacity that interfered with the performance of the executive function tests. Eligibility criteria were checked by a pediatrician.
2.3 Intervention
The exercise sessions were conducted on stationary bikes at the same gym, by trained physical educators, with a 3:1 student to instructor ratio. The HIIT and MICT intervention protocols were conducted three times a week, in the same gym and at different times for 12 weeks. The MICT session lasted 60 min with intensity progression every 4 weeks, established at 35%–55%, 45%–65% and 55%–75% of the heart rate reserve (HRR). The HIIT session lasted approximately 35 min, being 3 sets of 4 repetitions of 30 s of maximum effort, with 60 s of active recovery with self-selected speed, and 4 min of passive rest between sets. The caloric expenditure was measured by a heart monitor (Polar®, model A300), and was equivalent between the modalities (t = 0.863; p = 0.388). Both protocols were carried out on exercise bikes (Schwinn® IC). The CG was instructed to maintain their usual physical activities during the study period. At the end of the study, the exercise program was offered to these individuals.
2.4 Measurements
All assessments were carried out at a gym in the region where the study was carried out, in the initial phase period and after 12 weeks of intervention. The initial and final assessments were conducted during two participant visits. During the first visit, participants were evaluated by a pediatric physician, and anthropometric measurements, body composition analysis, and blood collection were performed. During the second visit, executive function tests were administered. The training programs were started after all assessments in the initial phase and ended 48 h before the final assessments.
Height and weight were measured for BMI calculations. Waist circumference was measured with an anthropometric tape with a precision of 0.1 cm. Body composition was evaluated using the bioelectrical impedance method, which used a tetrapolar analyzer with a frequency of 50 khz (Maltron BF906®). This procedure was performed in the morning, after a 12-hour fasting period. In addition, subjects were instructed to: (a) not consume liquids for 4 h before the test; (b) not exercise less than 12 h before testing; (c) urinate within 30 min before testing; (d) not consume alcohol within 48 h of testing; (e) not take the diuretic medication within seven days of testing; (f) not use metal accessories; and (g) wear light clothing. Fat-free mass (FFM) was calculated using gender-specific equations (18), and then the percentage of fat mass (%FM) was determined.
Somatic maturation was calculated using time-for-age prediction equations at peak height velocity (PHV) (19). The difference in years between PHV and chronological age was defined as a maturity offset value.
2.5 Executive function
Cognitive flexibility: the Trail Making Test was used to assess cognitive flexibility (20). The test consists of two steps, TMTA and TMTB. In both stages, the teenager must draw a path between several points in the shortest time possible. In the TMTA step, the individual must draw, in ascending numerical order, the path between 24 circles numbered 1–24. The TMTB step is the most complex stage, in which participants are required to draw an alternating sequence between numbers (1–12) and letters (A–L) as quickly and accurately as possible (21). For the analyses, cognitive flexibility was represented by subtracting the time spent in the TMTB from the TMTA, with the shorter the time, the better the test score.
Inhibitory control: The color and word Stroop test was used to assess inhibitory control. The test consists of two tasks, one for reading and the other for naming the color. In both, the stimuli are names of the colors “green”, “blue”, “grey”, and “pink” in Portuguese, printed in an incongruous color, totaling 112 words arranged in 4 columns (22). The test itself took place in two stages. In the first stage (STA) the adolescents were instructed to read all the words sequentially as quickly as possible and aloud. In the second stage (STB), the adolescents carried out the identification of colors sequentially, out loud, and as quickly as possible. For the analyses, time data and the percentage of correct answers in the STB test were used, as well as the reaction time in the STB test adjusted by the number of words (112 words) was calculated.
2.6 Blood analysis
Plasma BDNF 12-hours (night fasting) blood samples of approximately 20 mL of venous blood were collected in the morning from a forearm or antecubital vein, deposited in EDTA tubes, and kept on ice for approximately 60 min. After collecting and transporting the samples, they were centrifuged at 1,000 × g at 4 °C for 10 min and immediately stored at −80 °C. BDNF plasma concentration was measured using the human procartaplex simplex BDNF kit (Invitrogen), according to the manufacturer's instructions (ProcartaPlex™ Multiplex Immunoassay user guide), using MAGPIX® (Luminex duplex assay, Austin, TX, USA) equipment. Blood samples were analyzed clinical laboratory to measure glucose, insulin, and C-reactive protein (CRP) levels. The colorimetric enzymatic method was used for insulin (µIU/mL) measurements, glucose (mg/dL) was determined by the chemiluminescence method, and CRP (mg/L) was determined by the turbidimetry technique, using automated equipment.
2.7 Statistical analysis
Baseline sample characteristics were summarized as means and standard deviations, and differences between groups were examined using one-way ANOVA for continuous data. The verification of data normality was performed using the Shapiro–Wilk test and the homogeneity of variance was measured using the Levene test. Comparison of initial and post-intervention means on BDNF concentrations was calculated by two-way mixed factorial ANOVA with repeated measures, adjusted for sex and somatic maturation. Bonferroni posthoc was applied in all analyzes to verify differences between groups for variables with significant ANOVA. The effect size (ES) of the groups on changes in BDNF and executive function were calculated using linear regression by the difference between the post-intervention and baseline values, adjusted for sex and somatic maturation. Then, the standardization Cohen d (95%CI) was used to verify the individual effect of each group, as well as comparisons between groups (23). The clinical inference was conducted according to the magnitude of the standardized effect size (Cohen d), considering: trivial (|0.20|), possibly beneficial/harmful (|0.20–0.39|), beneficial/harmful (|0.40–0.79|) and very beneficial/harmful (|>0.80|) according to the direction of change of the evaluated outcome. It was considered an unclear effect when the effect overlaps the trivial values and the confidence intervals extrapolated both in harmful and beneficial effects (24). All statistical analyzes were performed using SPSS software version 24.0 (IBM Corp, Armonk, NY, USA). The significance level adopted was p < 0.05.
3 Results
Table 1 shows the baseline characteristics of the sample. There were no baseline differences between groups. Most participants (32 out of 53 or 63.4%) were classified as obesity, while the remaining participants were classified as overweight. There was no dropout in any group. All participants achieved a minimum of 70% adherence in training sessions.
Table 1. Baseline characteristics of the sample.
| Variable | Total sample (n = 53) | CG (n = 24) | MICT (n = 14) | HIIT (n = 15) | P |
|---|---|---|---|---|---|
| Mean (SD) | Mean (SD) | Mean (SD) | Mean (SD) | ||
| Age, years | 14.01 (2.09) | 14.43 (1.61) | 13.30 (2.30) | 14.00 (2.50) | 0.28 |
| PHV, years | 1.03 (1.8) | 1.21 (1.49) | 0.71 (1.88) | 1.00 (2.24) | 0.72 |
| Weight, kg | 72.90 (13.44) | 75.28 (12.54) | 66.90 (13.04) | 74.67 (14.33) | 0.15 |
| Height, cm | 160.38 (8.56) | 161.50 (7.65) | 157.07 (7.17) | 161.68 (10.63) | 0.24 |
| BMI, kg/m−2 | 28.23 (4.12) | 28.89 (4.63) | 26.85 (3.22) | 28.46 (3.95) | 0.33 |
| Percent body fat | 35.74 (6.95) | 35.53 (7.50) | 35.96 (5.43) | 35.87 (7.72) | 0.98 |
CG, control group; MICT, moderate-intensity continuous training; HIIT, high-intensity interval training; SD, standard deviation; PHV, peak of height velocity; BMI, body mass index.
3.1 Effect of groups on BDNF concentrations and executive function
Groups did not differ significantly at baseline in BDNF levels (F = 1.948, p = 0.154), cognitive flexibility (F = 1.479, p = 0.238) and inhibitory control (F = 0.725, p = 0.489). After 12 weeks (Table 2), the group-by-time interaction was significant for BDNF (F = 3.232, p = 0.048), cognitive flexibility (F = 7.804, p = 0.001), and for inhibitory control (STB: F = 5.603, p = 0.007), indicating that changes in BDNF levels and cognitive performance between groups differ significantly over time.
Table 2. Effect of intervention and control groups on cognitive flexibility, inhibitory control, and BDNF.
| Variables | GC (n = 24) | MICT (n = 14) | HIIT (n = 15) | Time by group | p | |
|---|---|---|---|---|---|---|
| Mean ± SD | Mean ± SD | Mean ± SD | F | |||
| Anthropometric variables | ||||||
| Weight, kg | baseline | 75.28 ± 12.54 | 66.90 ± 13.04 | 74.67 ± 14.33 | 0.94 | 0.38 |
| post | 75.38 ± 13.24 | 68.02 ± 12.98 | 75.18 ± 13.99 | |||
| Height, cm | baseline | 161.50 ± 7.65 | 157.07 ± 7.17 | 161.68 ± 10.63 | 1.16 | 0.03 |
| post | 162.11 ± 7.68 | 158.03 ± 7.36 | 162.91 ± 10.44 | |||
| BMI, kg/m−2 | baseline | 28.89 ± 4.63 | 26.85 ± 3.22 | 28.46 ± 3.95 | 0.94 | 0.44 |
| post | 28.70 ± 4.78 | 26.97 ± 3.01 | 28.25 ± 3.94 | |||
| Percent body fat | baseline | 35.53 ± 7.50 | 35.96 ± 5.43 | 35.87 ± 7.72 | 1.01 | 0.32 |
| post | 34.35 ± 8.51 | 36.14 ± 4.83 | 35.01 ± 8.48 | |||
| Cognitive flexibility | ||||||
| TMTA (s) | baseline | 31.19 ± 10.79 | 39.62 ± 15.81 | 34.24 ± 18.33 | 9.58 | <0.01 |
| post | 31.16 ± 10.01 | 27.60 ± 11.44* | 21.73 ± 8.47* | |||
| TMTB (s) | baseline | 74.66 ± 25.35 | 80.62 ± 24.04 | 123.68 ± 93.04a | 18.82 | <0.01 |
| post | 76.37 ± 33.99 | 64.44 ± 25.47* | 49.21 ± 22.68*a | |||
| TMTB-TMTA (s) | baseline | 43.47 ± 22.89 | 41.00 ± 22.66 | 89.57 ± 93.92 | 7.80 | <0.01 |
| post | 45.21 ± 30.72 | 36.74 ± 21.26 | 27.47 ± 18.82*a | |||
| Inhibitory control | ||||||
| STA (s) | baseline | 73.03 ± 15.95 | 75.57 ± 15.83 | 70.49 ± 15.97 | 0.90 | 0.41 |
| post | 75.85 ± 16.96 | 73.37 ± 17.77 | 69.87 ± 15.65 | |||
| STB (s) | baseline | 159.56 ± 41.96 | 182.29 ± 75.32 | 166.71 ± 75.32 | 5.60 | <0.01 |
| post | 149.99 ± 48.45 | 147.90 ± 50.14* | 127.06 ± 34.14* | |||
| Accuracy of answers (%) | baseline | 92.95 ± 4.26 | 92.02 ± 5.82 | 90.00 ± 9.13 | 3.02 | 0.06 |
| post | 94.46 ± 3.67 | 95.31 ± 3.95* | 95.68 ± 2.73* | |||
| Reaction time (s) | baseline | 1.42 ± 0.37 | 1.62 ± 0.67 | 1.48 ± 0.49 | 5.60 | <0.01 |
| post | 1.33 ± 0.43 | 1.32 ± 0.44* | 1.13 ± 0.30* | |||
| Blood analysis | ||||||
| BDNF (pg/mL) | baseline | 125.36 ± 77.04 | 130.2 ± 54.71 | 183.1 ± 123.97 | 3.23 | 0.04 |
| post | 124.75 ± 98.64 | 144.89 ± 70.57 | 255.61 ± 192.09*a | |||
| Insulin (μUI/mL) | baseline | 11.77 ± 5.20 | 18.05 ± 20.97 | 13.14 ± 9.93 | 0.53 | 0.59 |
| post | 12.21 ± 5.68 | 14.53 ± 5.69 | 13.56 ± 8.78 | |||
| Glucose (mg/mL) | baseline | 81.96 ± 6.20 | 84.82 ± 8.66 | 85.28 ± 8.39 | 0.56 | 0.57 |
| post | 81.83 ± 7.99 | 83.18 ± 5.15 | 86.29 ± 8.52 | |||
| CRP (mg/L) | baseline | 3.67 ± 8.68 | 3.20 ± 2.00 | 2.25 ± 1.42 | 0.36 | 0.70 |
| post | 2.45 ± 3.00 | 3.49 ± 3.01 | 2.45 ± 3.38 |
Results obtained by two-factor ANOVA with repeated measures (group × time), adjusted for sex and somatic maturation. CG, control group; HIIT, high-intensity interval training; MICT, moderate-intensity continuous training; BMI, body mass index; TMT, trial making test; ST, Stroop test; BDNF, Brain-derived neurotrophic factor; CRP, C-reactive protein; SD, standard deviation; s, seconds. a, different from CG; b, different from MICT; c, different from HIIT; *, time effect.
The effect of time revealed a significant increase in plasma BDNF level in the HIIT group after the 12-week intervention (Δ = 70.43 pg/mL, p = 0.003), whereas the CG showed no change (Δ = −3.09 pg/mL, p = 0.865). Although the MICT exhibited a modest, non-significant increase (Δ = 21.17 pg/mL, p = 0.391), post-hoc comparisons indicated no difference between HIIT and MICT. There was a significant improvement in cognitive flexibility in the HIIT group (Δ = −59.62s, p < 0.001), but not in the MICT (Δ = −9.32s; p = 0.806) and CG (Δ = 3.15s; p = 0.834). For inhibitory control, there was a significant improvement in the HIIT group (Δ = −39.88s, p < 0.001) and MICT (Δ = −31.55s, p = 0.001), but not for the CG (Δ = −11.08s, p = 0.099). The interaction between sex by group by time was not significant on BDNF values (F = 0.445, p = 0.508, and F = 1.339, p = 0.253), cognitive flexibility (F = 1.655, p = 0.204, and F = 0.097, p = 0.757) and inhibitory control (F = 0.021, p = 0.885, and F = 2.693, p = 0.107), which indicates that there were no effects of sex on changes in BDNF levels and executive function by protocol analysis.
3.2 The magnitude of effect on BDNF concentrations and executive function
There was a moderately significant effect on plasma BDNF levels for the HIIT group, which were all classified as beneficial, as well as possibly beneficial and non-significant for MICT, and trivial for CG (Figure 1). Moderate to large intervention effects for inhibitory control and cognitive flexibility were found for the MICT, which were classified as beneficial. In the HIIT group, large to very large intervention effects were observed for inhibitory control and cognitive flexibility, which were classified as beneficial and very beneficial. For the CG, however, a small non-significant effect was identified on inhibitory control and cognitive flexibility, and classified as trivial.

Large to very large intervention effects were observed in favor of HIIT compared to MICT and CG, considered beneficial (Figure 2). Moderate to large intervention effects were observed in favor of MICT compared to CG for inhibitory control and cognitive flexibility, which were all classified as beneficial. There were large to very large intervention effects in favor of HIIT compared to CG for inhibitory control and cognitive flexibility, which were classified as beneficial and very beneficial. When comparing the training groups, a small intervention effect in favor of HIIT on inhibitory control was noted, considered trivial, as well as a large intervention effect in favor of HIIT on cognitive flexibility, which was classified as beneficial.

4 Discussion
The main findings of the present study indicated that HIIT intervention was beneficial and promoted significant increases in plasma BDNF levels, as well as improvements in performance on executive function tests, compared to the CG. Although MICT also had positive effects on executive functions, only HIIT resulted in a significant increase in BDNF. These results suggest that the changes observed may be related to the type and intensity of the exercise protocol. Furthermore, the improvement in BDNF concentrations occurred in parallel with advances in executive functions, reinforcing the possible role of neurotrophic mechanisms in physically inactive adolescents with overweight and obesity. Additionally, in the MICT, improvements were observed only in inhibitory control, while cognitive flexibility did not show relevant changes, suggesting that moderate-intensity training may selectively influence some components of executive functions and that higher intensities may be necessary to promote broader cognitive benefits.
In adolescents with overweight and obesity, it is important to consider that excess adiposity is typically accompanied by low-grade systemic inflammation and increased oxidative stress, both of which are associated with reduced executive function and lower circulating BDNF (3, 25–28). Although such mechanisms are linked to adiposity, the cognitive and neurotrophic improvements observed in our study appear to result primarily from the direct effects of exercise, rather than from changes in weight or body composition, which did not differ significantly across groups. Evidence indicates that aerobic exercise can modulate neurobiological pathways independently of reductions in adiposity, enhancing cerebral blood flow, stimulating the release of myokines such as BDNF, and improving antioxidant capacity (3, 25–28). Thus, the improvements in executive function and the increase in BDNF observed particularly in the HIIT group are more plausibly attributable to exercise-induced neurobiological adaptations rather than to adiposity-related changes.
Indeed, we observed that the practice of high-intensity physical exercise promotes a moderate increase in plasma BDNF in physically inactive overweight and obese adolescents. However, our non-significant results regarding MICT were not consistent with previous studies that reported increased serum BDNF concentrations, but the studies were performed in non-obese adolescents (10). On the other hand, our findings corroborate the results of a previous study in adolescents with obesity (29). Therefore, a possible explanation for this discrepancy can be related to the study population. Goldfield et al. (29) compared the effect of MICT, resistance training, or combined on serum BDNF in 304 adolescents with obesity for 6 months. As in our study, it was reported that there were no significant changes in BDNF after MICT intervention. While studies with non-obese adolescents showed an increase in serum BDNF after aerobic exercise (30, 31). Apparently, overweight and obese adolescents may exhibit a blunted BDNF response to moderate-intensity aerobic exercise compared to their non-obese peers. Therefore, a higher-intensity aerobic stimulus may be necessary to elicit significant changes in BDNF levels in this population.
Although baseline BDNF concentrations did not differ significantly between groups, the wide inter-individual variability observed is consistent with previous evidence showing that adolescents with overweight and obesity present heterogeneous inflammatory and metabolic profiles, which directly influence circulating BDNF levels (25–28). Likewise, the poorer baseline TMT-B performance in the HIIT group likely reflects natural variability related to differences in executive function frequently reported in this population (3, 26, 27), especially considering the absence of randomization. These baseline patterns therefore appear to represent expected heterogeneity rather than systematic group differences.
Furthermore, obesity has been inversely associated with plasma BDNF concentrations (25) and executive function (3, 26, 27). According to Hristova et al. (28), the lower peripheral concentrations of BDNF observed in individuals with obesity may be a consequence of the chronic low-grade inflammatory state characteristic of this condition. Elevated pro-inflammatory cytokines may disrupt the balance between immunosuppressive and immunostimulating pathways, reducing the bioavailability of BDNF. Likewise, BDNF has also been identified as a key component of the hypothalamic pathway that modulates body weight control, glucose metabolism, food intake, and energy homeostasis, which can lead to obesity (32) and type 2 diabetes (33). Thus, there is evidence to indicate significantly lower baseline BDNF concentrations in overweight/obese people compared to adults (34) and non-obese youth (35). Collectively, these results suggest that BDNF may play an important role in the pathophysiology of obesity.
Our study was the first, to our knowledge, to examine the effects of different physical exercises on plasma BDNF, whereas previous studies in adolescents have assessed serum BDNF (29, 31). The difference between the plasma and serum BDNF analyses reveals that the serum concentration may represent the BDNF stored in platelets, therefore, the serum responses to exercise may not be explained by a cerebral source. On the other hand, the plasma portion of BDNF circulates freely and may be bioavailable to cross the blood-brain barrier (36). Increased BDNF in the brain may result in better neuronal survival and synaptogenesis, which may indicate structural changes and positive brain functions (37). An interesting fact is that platelets cannot cross the blood-brain barrier, therefore, exercise can play a key role in the release of BDNF stored in platelets in plasma (38). Thus, Lommatzsch et al. (39) observed that plasma BDNF concentrations are subject to reduction with increasing weight and age, whereas serum concentrations do not. This highlights the importance of physical exercise for both the treatment and prevention of overweightness (40) as well as in the maintenance and improvement of cognitive and academic performance (41).
An additional worthy finding of the present study is that only HIIT promoted significant and superior changes on plasma BDNF compared to MICT group and CG. This reinforces the hypothesis that changes in plasma BDNF induced by physical exercise may be related to intensity (12, 42) and not the exercise volume (9). In the study of Jeon et al. (31) it was possible to observe the indication of the effect of different intensities of physical exercises on the serum concentrations of BDNF. After comparing 12 weeks of continuous exercise at light, moderate and vigorous intensities, the authors observed positive effects of exercises at a moderate and vigorous intensity, with greater effect for the vigorous-intensity group. Reycraft et al. (43) reported that higher concentrations of BDNF were observed after a high-intensity interval training session compared to continuous training at the moderate-vigorous intensity in adults. In addition, there is evidence of a beneficial relationship between lactate level and cognitive performance; in this sense, the production of lactate would cross the blood-brain barrier, feeding the neurons and stimulating the secretion of BDNF (44).
The role that intensity plays in the effects of chronic aerobic exercise interventions in young people remains poorly studied and poorly understood. Given the present evidence that HIIT conducted on cycle ergometers may be preferable to MICT prescriptions on plasma BDNF concentrations in overweight and obese adolescents. However, the effectiveness of different HIIT interventions performed through running or water activities, such as frequency and duration, variables that need to be evaluated to determine whether they have a positive impact on BDNF in obese youth. Whereas there is evidence that outdoor exercise outdoors and a connection to nature can enhance cognitive processes and well-being compared to exercising indoors (45) it would also be important to assess the effects that outdoor exercise has on BDNF levels in adolescents.
Physiological mechanisms, including increased cerebral blood flow, blood–brain barrier disruption, and changes in neurotransmitter release, are suggested as explanations for the relationship between exercise and cognition (46). Our study also reinforces the hypothesis that BDNF may be one of the mechanisms by which the practice of physical exercise promotes benefits on cognitive performance in overweight and obese adolescents. The findings corroborate previous studies conducted with MICT in non-obese adolescents (29, 31). However, there is still a need for further studies to analyze the relationship between BDNF concentrations, executive function, and physical exercise in normal-weight and overweight/obese adolescents.
The current study has several strengths and limitations. Strengths include comparing two types of physical exercise with a CG, which provides high-quality evidence to support the conclusions. This was the first study to comparatively examine the effects of MICT and HIIT on plasma BDNF levels and executive function in overweight and obese adolescents, a population known to be at high risk for medical and psychosocial comorbidities, and impaired executive functioning (3). All statistical analyzes were controlled for sex and somatic maturation. In addition, the volume and intensity of training prescribed to participants were carefully controlled. With the support of this research, it is expected to highlight the importance of policies for the implementation of regular physical activities for children and adolescents, as this is a significant period in which the development of brain function, learning, and cognitive ability can be improved.
Some limitations should be taken into account. Firstly, the intervention period was relatively short, and there was no long-term follow-up. Secondly, the sample was not randomized and was relatively small. Additionally, we did not assess the socioeconomic status of the participants. Furthermore, we did not evaluate the serum portion of BDNF, which could have provided more insight into the effects of chronic exercise on both plasma and serum components. We also did not analyze the executive function domain, specifically working memory. Moreover, it's important to note that implementing this intervention may vary depending on the resources available in different schools. Access to bikes, gym facilities, or similar resources may be necessary for this protocol. Therefore, it's crucial to acknowledge that feasibility may be limited in schools with resource constraints, and alternative approaches should be explored to promote physical activity and cognitive development in such settings. Although increases in BDNF and improvements in executive function occurred concurrently, this study was not designed or powered to test associative relationships between these outcomes.
Future research with larger samples and appropriate designs is needed to investigate whether exercise-induced changes in BDNF are directly related to cognitive improvements. Additionally, future studies would benefit from examining a broader range of biochemical markers to deepen the understanding of the physiological pathways underlying exercise-induced neurocognitive changes. Although our study focused on BDNF, incorporating other relevant biomarkers in future investigations may help clarify whether the cognitive and neurotrophic adaptations observed are driven primarily by direct neural mechanisms or also influenced by broader metabolic responses. Nevertheless, we hope our findings contribute to understanding how physical activity influences BDNF and executive function in overweight and obese adolescents, and future studies should address these limitations to further clarify these mechanisms.
5 Conclusions
In conclusion, we observed that three months of HIIT promoted a moderate increase in resting plasma BDNF levels and an improvement in cognitive performance in a sample of physically inactive adolescents with overweight and obese. Although less effective than HIIT, MICT was beneficial for cognitive performance; however, it did not produce significant changes in BDNF levels. In contrast, HIIT promoted significant improvements in both BDNF concentrations and executive function. Thus, further studies are needed to verify these initial findings and further elucidate the effects that various exercise modalities, doses, and environments have on peripheral concentrations of resting plasma and serum BDNF, as well as their relationship with concomitant cognitive function in an attempt to optimize exercise prescriptions in high-risk populations.
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Footnotes
Edited by: Boris Schmitz, Witten/Herdecke University, Germany
Reviewed by: Alexandre Pastoris Muller, Federal University of Santa Catarina, Brazil
Christine Mermier, University of New Mexico, United States
Abbreviations BDNF, brain-derived neurotrophic factor; BMI, body mass index; CG, control group; FFM, fat-free mass, FM, fat mass; MICT, moderate-intensity continuous training; HIIT, high-intensity interval training.
Statements
- Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Funding
The author(s) declared that financial support was not received for this work and/or its publication.
- Data availability
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
- Ethics approval
The studies involving humans were approved by The study was approved by the Ethics Committee of UniDomBosco (CAAE:62963916.0.0000.5223) and registered in the Brazilian Registry of Clinical Trials (protocol: RBR-6343y7). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants' legal guardians/next of kin.
- Author contributions
FM-J: Investigation, Writing – review & editing, Resources, Conceptualization, Data curation, Formal analysis, Writing – original draft, Methodology. CB: Formal analysis, Data curation, Writing – review & editing. MT: Methodology, Conceptualization, Writing – review & editing, Data curation, Funding acquisition, Resources. TT: Data curation, Writing – review & editing. PC: Methodology, Data curation, Conceptualization, Resources, Writing – review & editing, Funding acquisition. JM: Supervision, Writing – review & editing. BP: Writing – review & editing, Supervision. RR: Writing – review & editing, Supervision. NL: Project administration, Methodology, Conceptualization, Writing – review & editing, Resources, Funding acquisition.
- Acknowledgements
This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação para a ciência e tecnologia (FCT: SFRH/BSAB/142983/2018 and UID/DTP/00617/2019), Programa de Bolsas Santander Universidades 2018, Programa Pesquisa Para o SUS (PPSUS—edital—CP 01/2016) via Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Estado do Paraná (Decit/ MS) and Secretaria da Saúde do Estado do Paraná (SESA-PR). The last author (NL) was supported by the CNPq Scholarship for Productivity, the UFPR Senior Research Scholarship and Brazilian International Project 402698/2024-0 - Edital 16/2024 CNPq.
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Citation
Menezes-Junior, F. J. d., et al. (2026). Effects of continuous and interval training on brain-derived neurotrophic factor concentrations and executive function in physically inactive adolescents with overweight and obesity. Frontiers in Adolescent Medicine, Volume 4. https://doi.org/
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- 4 - 2026
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© 2026 Menezes-Junior, Brand, Tadiotto, Tozo, Corazza, Mota, Pereira, Rosário and Leite.
License: https://creativecommons.org/licenses/by/4.0/
*Correspondence: Maiara Cristina Tadiotto
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