Introduction

According to the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), as of 2021, approximately 18% of children and adolescents aged 5–14 years worldwide were classified as having either overweight or obesity, encompassing both categories1. Among these individuals, nearly 70% are likely to sustain obesity into adulthood1, significantly elevating their risk of chronic physiological and psychological disorders2. Living with obesity over the long-term is a well-established risk factor for various metabolic diseases, including dyslipidemia, type 2 diabetes mellitus, and cardiovascular diseases3, and is also associated with irregular menstruation stemming from polycystic ovary syndrome (PCOS) in females4. In addition, people with obesity often experience psychological comorbidities, such as depression, anxiety, and low self-esteem, which significantly contribute to an increased risk of premature mortality5. These psychological burdens may also discourage physical activity and reinforce sedentary behavior, thereby creating a vicious cycle that perpetuates poor health outcomes2. Therefore, early intervention and management for childhood and adolescence living with obesity are crucial to prevent related complications.

Increased sedentary behaviors and poor dietary habits are primary contributors to obesity in children and adolescents6. Excess adiposity leads to the overproduction of leptin, an appetite-regulating hormone secreted by adipose tissue, resulting in leptin resistance7. Under normal conditions, leptin helps regulate body weight by suppressing appetite and promotes energy expenditure8. However, in individuals with obesity, chronically elevated leptin levels are accompanied by impaired leptin receptor signaling and attenuated central leptin activity, a condition referred to as leptin resistance9. This dysregulation disrupts appetite regulation and energy homeostasis, contributing to obesity progression and metabolic dysfunction. Leptin resistance therefore aggravates both psychological and physiological complications in this population10. In children and adolescents with obesity, leptin resistance is recognized as a critical pathophysiological mechanism that perpetuates excess adiposity and elevate the risk of chronic diseases in adulthood. Notably, elevated leptin concentrations in this population serve as clinical biomarkers future metabolic disorders11. Therefore, promoting physical activity and balanced dietary habits during early life is crucial for enhancing leptin sensitivity and mitigating long-term health risks.

Regular exercise represents a key non-pharmacological strategy for effectively mitigating leptin resistance12. Among various exercise modalities, plyometric exercise, which utilizes repetitive stretch shortening cycles to enhance muscle strength, bone loading, and metabolic demand, has shown particular promise for adolescents due to its dual effects on muscle fitness and growth stimulation13. Increased physical activity facilitates quantitative and qualitative muscle development and reduces body fat mass14, enhancing leptin sensitivity through reduced expression of Suppressor Of Cytokine Signaling 3 (SOCS3) and Protein tyrosine phosphatase 1B (PTP1B), major inhibitors of leptin signaling within muscle tissues15. Studies involving adolescents with obesity and animal models have consistently demonstrated that regular exercise effectively reduces body fat and circulating leptin levels while increasing muscle mass and leptin sensitivity16,17. Furthermore, myokines secreted from skeletal muscles during exercise exhibit anti-inflammatory properties, thereby reducing systemic chronic inflammation and directly contributing to improved leptin sensitivity18. Thus, enhancing leptin sensitivity through regular exercise in children and adolescents with obesity is crucial for breaking the vicious cycle and maintaining long-term health.

However, previous studies primarily focused on animal models of obesity16 or were limited to examining individual physiological parameters such as leptin and adipokine concentration19, growth hormone, and myokines20. Comprehensive studies exploring the integrated physiological impact of regular exercise on growth hormones, appetite-regulating hormones, myokines, and adipokines among children and adolescents with obesity and leptin resistance remain scarce. Therefore, the present study aims to address the limitations of previous research by comprehensively analyzing the integrated effects of regular exercise on growth hormones, appetite-regulating hormones, myokines, and adipokines in adolescents with obesity and leptin resistance. Ultimately, this study seeks to provide fundamental data for establishing more effective and systematic intervention strategies applicable to the management of children and adolescents with obesity.

Methods

Study design and participation

This study complied with the ethical standards of the Declaration of Helsinki and was approved by the Institutional Review Board of Kangwon National University (KWNUIRB-2023-05-007) on May 25, 2023. Adolescents with Obesity and Leptin Resistance were recruited between August 1, 2023, and October 12, 2024. It was retrospectively registered with the Korea Clinical Trials Registry (KCT0010749; July 11, 2025). Written informed consent was obtained from all participants and their legal guardians. Participation was entirely voluntary, and participants were informed that they could withdraw from the study at any time without consequences. However, the study was not registered in a clinical trial registry prior to participant enrollment, which we acknowledge as a limitation. Sixty adolescents with obesity and leptin resistance (body fat percentage ≥ 30%; leptin ≥ 30 ng/mL), were recruited, comprising 30 males and 30 females. The mean age was 11.9 ± 0.8 years for males and 13.0 ± 1.0 years for females. Based on chronological age, participants were estimated to correspond to Tanner stages 2–3, although direct Tanner staging was not performed. Sample size was calculated using G*Power software (version 3.1.9.7; Heinrich Heine University, Düsseldorf, Germany). Assuming an α = 0.05, power = 0.80, and a medium effect size (f = 0.25), the minimum total sample size required was 48 participants. To account for potential a 20% dropout rate, a total 60 participants were enrolled. Inclusion criteria were: (1) absence of medical or musculoskeletal conditions limiting participation in plyometric exercise and (2) voluntary agreement to participate with guardian consent. Exclusion criteria were: (1) use of weight-loss medication, (2) cardiovascular or cardiopulmonary dysfunction, and (3) musculoskeletal injuries within the previous six months. At baseline, participants underwent body composition and blood assessments after an overnight fast at the Exercise Physiology Laboratory, Department of Sports Science. Participants were then randomized by gender into either a control group (CON, n = 15 per gender) or a plyometric exercise group (PE, n = 15 per gender) using simple randomization with opaque envelopes. Outcome assessors were blinded to group allocation to minimize measurement bias. The random sequence was generated by an independent researcher not involved in participant recruitment or assessment, and group allocation was implemented by a separate assistant using opaque, sealed envelopes to ensure allocation concealment. The 12-week intervention was followed by identical post-testing. Twelve participants withdrew during the study (male: CON, n = 3; PE, n = 3; female: CON, n = 3; PE, n = 3). For ethical transparency, control group participants were given the option to receive the same exercise intervention after the study period. Although offered, no one participated post-intervention. Participants assigned to the control group were instructed to maintain their usual daily routines and were explicitly advised not to engage in any structured or regular physical exercise throughout the 12-week study period. Among those who completed the study, session attendance rates exceeded 95%.

The specific contents of the study design are shown in Fig. 1.

Fig. 1
figure 1

Study design.

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Measurement of body composition

The Body composition variables were assessed using a bioelectrical impedance analyzer (BIA) (Inbody 720 Body Composition Analyzer, Biospace, Seoul, Republic of Korea). Measurements were performed with participants barefoot and wearing light clothing, after removing shoes, socks, and heavy accessories. Weight (kg), fat mass (kg), and skeletal muscle mass (kg) were recorded to the nearest 0.1 kg. Body fat percentage was estimated based on impedance values obtained from multiple frequencies. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared (kg/m²).

Hematological analysis

Fasting venous blood samples were collected from all participants at baseline and 12 weeks after the intervention. Participants were instructed to refrain from vigorous physical activity for at least 24 h prior to each visit and to maintain normal daily activities without engaging in strenuous exercise. They were also advised to obtain a minimum of 7 h of sleep the night before sample collection. Compliance with these instructions was verbally confirmed on the day of the visit. On each assessment day, participants arrived at the laboratory after a 12-hour overnight fast. Blood samples were collected at 08:00 from the antecubital vein into serum separator tubes (SST). The samples were allowed to clot at room temperature for 30 min before centrifugation. After clotting, the samples were centrifuged at 3,500 g for 10 min at room temperature to obtain serum. The separated serum samples were then aliquoted and stored at − 80 °C until further analysis. Serum levels of growth hormone such as growth hormone(GH), Insulin-like Growth Factor 1 (IGF-1), and Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3)(DY1067, DY291, and DY675: R&D Systems, Minneapolis, MN, USA), appetite hormone such as Insulin(440132, Beckman Coulter, California, CA, USA), leptin, and ghrelin(DY398, and DY8149-05: R&D Systems, Minneapolis, MN, USA), myokine such as irisin, myostatin, and follistatin (DY9420-05, DY788-05, and DY669: R&D Systems, Minneapolis, MN, USA), and adipokine such as adiponectin, and adipose tissue-derived cytokine and tumor necrosis factor-alpha (TNF-α) (DY1065, and DY210: R&D Systems, Minneapolis, MN, USA) were measured using DuoSet TM enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA) according to the manufacturer’s instructions.

Measurement of muscle fitness

A digital handgrip dynamometer (GRIP-D 5101; TAKEI, Co., Tokyo, Japan) was used to measure right and left grip strength. All measurements were entered into an electronic card and transmitted to a computer. Abdominal muscle endurance was assessed by counting the maximum number of sit-ups performed within 30 s. An isokinetic dynamometer (Humac Norm Testing and Rehabilitation, CSMi Medical & Solutions, Stoughton, MA, USA) was utilized to assess unilateral knee maximum strength, muscle power, and endurance. Maximum knee strength(peak torque) was evaluated through isokinetic extension and flexion tests performed at an angular velocity of 60°/s for 3 repetitions. Muscle power was assessed using the same extension and flexion tests conducted at an angular velocity of 180°/s for 15 repetitions. During the assessment, the lateral epicondyle of the femur was precisely aligned with the rotational axis of the dynamometer to ensure proper joint positioning. The participant’s body was stabilized using adjustable straps to minimize extraneous movement and isolate knee joint activity. The seat height, footrest, and shoulder pads were adjusted according to each participant’s body dimensions to maintain optimal posture and alignment. Additionally, the trunk was stabilized by securing both the upper and lower body, and participants were instructed to firmly grasp the handles of the chest pad with both hands to prevent compensatory movements. Prior to data collection, participants completed a familiarization session to practice the testing procedures and ensure consistent performance. The primary outcome variables included peak torque for knee flexion and extension, normalized to body weight (Nm/kg)14.

Exercise intervention

We established plyometric training as the primary exercise intervention in this study. The plyometric training protocol consisted of exercises conducted on nonconsecutive days, three times per week (Monday, Wednesday, and Friday) for 12 weeks. Each training session was structured into three segments: a 10-minute warm-up, a 50-minute main exercise session, and a 10-minute cool-down period. This plyometric exercise program was adapted based on methodologies described in previous study13. The training volume initially comprised 20–24 jumps per session during the first 4 weeks, progressively increasing to 72–80 jumps per session by the final 4 weeks of intervention. Additional training drills, including sprinting exercises (e.g., A-skips, butt kicks) and throwing movements, were incorporated into the program. Participants were given sufficient recovery intervals between exercises and sets to maintain performance fitness and safety. If participants displayed signs of fatigue or compromised technique, exercises were immediately discontinued. Subjects were instructed to perform each plyometric movement with maximal explosive effort. The exercise intensity and complexity were progressively increased every 4 weeks by adjusting repetitions or introducing more advanced jump variations. Exercise intensity was objectively monitored using Polar heart-rate monitors, targeting an energy expenditure of 300–350 kcal per training session. Target heart rate zones were set at 50–60% HRmax for weeks 1–4, 60–70% HRmax for weeks 5–8, and 70–80% HRmax for weeks 9–12. Real-time heart rate data were displayed on table PCs connected to the Polar system and continuously monitored by exercise physiologist. If participants exceeded their target heart tare zone, exercise intensity was immediately reduced to maintain safety and compliance to the prescribed intensity. All exercise sessions were conducted under the supervision of a certified exercise physiologist.

Specific contents of the exercise program are shown in Table 1.

Statistical analysis

All results are reported as mean ± standard deviation. Statistical analyses were performed using SPSS version 29.0 (SPSS Inc., Chicago, IL, USA). The assumption of normality was verified using the Shapiro-Wilk test, and all variables met the criteria for normal distribution. A two-way repeated measures analysis of variance (ANOVA) was used to evaluate the main effects of group and time, as well as their interaction. When significant interaction effects were observed, post-hoc analyses were conducted using Bonferroni-adjusted pairwise comparisons for between-group differences, and paired-sample t-tests for within-group differences over time. Statistical significance was set at α = 0.05. Non-significant trends are reported up to p = 0.1 in the text.

Effect sizes were calculated using Cohen’s d to quantify the magnitude of intervention effects. First, the mean difference between post- and pre-intervention values was calculated by subtracting the pre-intervention mean from the post-intervention mean. The pooled standard deviation was then computed as the square root of the average of the squared pre- and post-intervention standard deviations. Finally, Cohen’s d was obtained by dividing the mean difference by the pooled standard deviation. Effect sizes were interpreted as small (d < 0.2), medium (d ≥ 0.5), and large (d ≥ 0.8) according to conventional criteria21.

Table 1 Exercise program.
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Results

Change in body composition

Changes in body composition parameters are presented in Table 2. Two-way repeated-measures ANOVA indicated significant group-by-time interaction for height (p = 0.039). Significant main effects of time were observed for height (p < 0.001), muscle mass (p = 0.001), fat mass (p = 0.001), percent body fat (p < 0.001), and BMI (p = 0.037). Paired t-tests revealed that MPE (p < 0.05) group exhibited significant improvements in height, muscle mass, fat mass, percent body fat, and BMI after 12 weeks compared to baseline. Specifically, height and muscle mass increased by 0.91% and 4.3%, respectively, while fat mass, percent body fat, and BMI decreased by 6.0%, 5.9%, and 1.9% in the MPE group. These changes corresponded to small to moderate effect sizes(Cohen’s d = 0.26 for height, 0.27 for muscle mass, -0.32 for fat mass, -0.45 for percent body fat, and − 0.21 for BMI). Additionally, FPE group exhibited significant increase in height(p < 0.05), muscle mass(p < 0.05), fat mass(p < 0.001), percent body fat(p < 0.001), and BMI(p < 0.05) after 12 weeks compared to baseline. Height and muscle mass increased by 0.56% and 0.3%, respectively, while fat mass, percent body fat, and BMI decreased by 4.1%, 3.2%, and 2.1% in the FPE group. with small effect sizes (d = 0.14 for height, d = 0.02 for muscle mass, d = -0.17 for fat mass, d = -0.27 for percent body fat, and d = -0.19 for BMI), indicating statistically meaningful and potentially clinically relevant effects.

Table 2 Change in body composition.
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Change in muscle fitness

Changes in muscle fitness parameters are presented in Table 3. Two-way repeated-measures ANOVA revealed no significant group-by-time interaction effects. However, significant main effects of time were observed for right and left grip strength (both p < 0.001), right and left knee extension and flexion peak torques (all p < 0.001), right knee flexion muscle power (p = 0.002), and left knee flexion muscle power (p < 0.001). Paired t-tests indicated that the MPE group showed significant increase in right grip strength(p < 0.001), left grip strength(p < 0.05), left knee extension peak torque, right and left knee flexion peak torque, and right and left knee flexion muscle power after 12 weeks compared to baseline (p < 0.05). Specifically, right and left grip strength increased by 9.92% and 11.14%, corresponding to moderate to large effect sizes (Cohen’s d = 0.75 and 0.54). Left knee extension torque by 12.27% with a moderate effect size (d = 0.56). Right and left knee flexion torque by 25.09% and 17.35% representing large and moderate effect sizes (d = 0.98 and 0.68), and right and left knee flexion muscle power by 16.57% and 21.43% with moderate to large effect sizes (d = 0.74 and 1.17), respectively, in the MPE group. Additionally, the FPE group showed significant increase in right grip strength(p < 0.05), left grip strength(p < 0.05), right knee extension peak torque (p < 0.001), right knee flexion peak torque, and left knee flexion muscle power (p < 0.05) after 12 weeks compared to baseline. Specifically, right and left grip strength increased by 7.39% and 12.51% corresponding too small to moderate effect sizes (d = 0.26 and 0.43), right knee extension torque by 11.60% with a moderate effect size (d = 0.56), right knee flexion torque by 10.25%, and left knee flexion muscle power by 9.97% in the FPE group with a small effect size (d = 0.33). Finally, the FCON group exhibited significant increase in left grip strength(p < 0.05), right knee flexion peak torque after 12 weeks compared to baseline (p < 0.05). Specifically, left grip strength and right knee flexion torque increased by 4.24% and 11.48% corresponding to small effect sizes (d = 0.12 and 0.50), respectively, in the FCON group.

Change in in growth hormone factors

Changes in growth hormone factors parameters are presented in Fig. 2A. Two-way repeated-measures ANOVA revealed no significant group-by-time interaction effects. Significant main effects of time were observed for GH (p = 0.007), and IGF-1 (p = 0.023). Paired t-tests revealed that MPE and FPE groups (p < 0.05) exhibited significant improvements in GH after 12 weeks compared to baseline. Specifically, GH levels increased by 28.3% in the MPE group corresponding to a large effect size (d = 0.98) and 19.5% in the FPE group also indicating a large effect size (d = 1.04). Additionally, the MPE group (p < 0.05), FPE group (p < 0.001) exhibited significant improvements in IGF-1 after 12 weeks compared to baseline. IGF-1 levels increased by 21.4% in the MPE group and 18.9% in the FPE group, corresponding to moderate effect sizes (d = 0.51 and 0.54, respectively).

Table 3 Change in muscle fitness.
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Change in appetite hormone factors

Changes in appetite hormone factors parameters are presented in Fig. 2B. Two-way repeated-measures ANOVA indicated significant group-by-time interaction effects for leptin (p < 0.001). Significant main effects of time were observed for insulin (p < 0.001), and leptin (p < 0.001). Paired t-tests revealed that MPE and FPE groups (p < 0.05) exhibited significant improvements in insulin after 12 weeks compared to baseline. Specifically, insulin levels decreased by 36.7% in the MPE group corresponding to a large effect size (d = -0.86), and 42.6% in the FPE group, with a moderate to large effect size (d = -0.73). Additionally, the MPE and FPE groups (p < 0.001) exhibited significant improvements in leptin after 12 weeks compared baseline with very large effect sizes (d = -1.86 and − 1.93), but the FCON group exhibited significant deterioration in leptin after 12 weeks. Leptin levels decreased by 24.6% in the MPE group and 25.7% in the FPE group, while it increased by 12.4%in the FCON group with a large effect size (d = 1.66).

Change in myokine factors

Changes in myokine factors parameters are presented in Fig. 2C. Two-way repeated-measures ANOVA indicated significant group-by-time interaction effects for myostatin (p = 0.036). Significant main effects of time were observed for myostatin (p = 0.004), and follistatin (p = 0.031). Paired t-tests revealed that MPE and FPE groups (p < 0.001) exhibited significant improvements in myostatin after 12 weeks compared to baseline. Specifically, myostatin levels decreased by 15.9% in the MPE group corresponding to a moderate to large effect size (Cohen’s d = -0.73), and 9.7% in the FPE group, indicating a moderate effect size (d = -0.48). Additionally, the MPE group (p < 0.05) exhibited significant improvements in follistatin after 12 weeks compared to baseline. Follistatin levels increased by 15.1% in the MPE group with a 15.1% increase, reflecting a large effect size (d = 1.10).

Change in adipokine factors

Changes in adipokine factors parameters are presented in Fig. 2D. Two-way repeated-measures ANOVA indicated significant group-by-time interaction effects for adiponectin (p = 0.011). Significant main effects of time were observed for adiponectin (p = 0.002). Paired t-tests revealed that MPE (p < 0.05), and FPE (p < 0.001) groups exhibited significant improvements in adiponectin after 12 weeks compared to baseline. Specifically, adiponectin levels increased by 13.7% in the MPE group (d = 0.68) and 27.6% in the FPE group (d = 0.68), indicating moderate to very large effect sizes, respectively.

Fig. 2
figure 2

(A) Change in growth hormones. (B) Change in appetite hormones. (C) Change in myokine factors. (D) Change in adipokine factors. Values are expressed as Mean ± SD. MCON, Male Control, MPE, Male Plyometric Exercise, FCON, Female Control, FPE, Female Plyometric Exercise; Analyzed by Two-way repeated ANOVA Interaction effect: #p < 0.05, ###p < 0.001; paired t-test: *p < 0.05; ***p < 0.001; Effect sizes were calculated using Cohen’s d and interpreted as small (d < 0.2), medium (d ≥ 0.5), and large (d ≥ 0.8) to evaluate practical significance.

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Discussion

Childhood and adolescents with obesity disrupt in endocrine signaling pathways such as the GH-IGF-1 axis and insulin signaling, leading to impaired growth, decreased muscle synthesis, excessive fat accumulation, and increased risk of early-onset metabolic disorders22. Chronic elevation of leptin further induces leptin resistance, disturbing metabolic and growth-related dysfunctions6. Consequently, leptin resistance exacerbates disturbances in endocrine signaling, thereby sustaining excess adiposity and impairing both metabolic function and growth-related health. To prevent obesity induced leptin resistance and associated growth-related impairments in adolescents, plyometric exercise may serve as an effective and practical intervention strategy. Therefore, this study investigated the effects of a 12-week plyometric training program on body composition, growth-related hormones, muscle fitness, and metabolic markers in adolescents with obesity and leptin resistance. The main findings were that plyometric training significantly increased GH and IGF-1 levels, improved height and muscle function, reduced body fat, and favorably modulated hormonal responses by decreasing leptin and insulin while increasing adiponectin.

Regular exercise increases energy expenditure, reduces body fat, and promotes muscle protein synthesis, thereby enhancing muscle mass and fitness14. Plyometric exercise, which leverages the stretch reflex mechanism, is recognized as optimal for adolescents, as it effectively combines improvements in muscle strength, bone health, growth stimulation, and fat reduction13. In this study, significant improvements in height, body fat percentage, BMI, muscle mass, and muscle fitness were observed post-intervention, irrespective of gender (Tables 2 and 3). These findings effectively address the limitations associated with isolated aerobic or resistance exercise treatments23,24, demonstrating meaningful physiological and clinical benefits of plyometric-based combined exercise on body composition in adolescents with obesity. Plyometric exercise utilizes repetitive stretch-shortening cycles, effectively increasing energy expenditure and promoting muscle protein synthesis, likely explaining the observed reductions in body fat and increases in muscle mass. These body composition changes were accompanied by small to moderate effect sizes (Cohen’s d = 0.26–0.45), indicating physiologically relevant improvements in height fat mass, and BIM, even within a relatively short interventions period. Improvements in body composition also play a crucial role in restoring normal GH-IGF-1-insulin signaling, vital for linear growth in adolescents. Interestingly, this study clearly demonstrates that regular plyometric exercise can activate the GH-IGF-1-insulin axis and positively influence height growth even in adolescents with persistent clinical obesity (≥ 30% body fat). GH (MPE 0.98, PME 1.04), IGF-1 (MPE 0.51, PME 0.54) levels improved with large to moderate effect sizes, suggesting robust activation of the somatotropic axis. Similarly, insulin (MPE − 0.84, PME − 0.73), leptin (MPE − 1.86, PME − 1.93) levels decreased with large to very large effects, indicating strong endocrine adaptations associated with enhanced leptin sensitivity and improved metabolic regulation. These results are consistent with previous findings in obese children treated with growth hormone for three months, in which plasma leptin concentrations showed parallel improvements25. The increase in GH appears to be involved not only in linear growth but also in appetite regulations, and our findings suggest a strong association between these mechanisms.

Generally, leptin resistance associated with obesity suppresses GH secretion and GH receptor (GHR) expression, reducing IGF-1 production and impairing longitudinal skeletal growth by limiting growth plate chondrocyte proliferation and differentiation26. Thus, the large reduction in leptin (d = -1.86 to -1.93) likely reflects improved receptor sensitivity, which may have facilitated the normalization of GH and IGF-1 secretion and contributed to the restoration of the GH-IGF-1 axis in growing adolescents27. Leptin plays a permissive role in linear growth by modulating hepatic GHR sensitivity and directly stimulating IGF-1 synthesis28. When leptin sensitivity improved, it may further potentiate GH-IGF-1 axis activation independent of GH concentrations29. Collectively, these findings emphasize that plyometric exercise elicits large endocrine adaptations particularly within the GH-IGF-1-insulin axis and leptin signaling that jointly support linear growth and metabolic restoration in adolescent with obesity. These improvements are likely attributable to repeated stretch-shortening stimuli inherent in plyometric exercise, directly enhancing growth plate chondrocyte proliferation and linear growth30. GH promotes growth plate chondrocyte proliferation and IGF-1 synthesis, while IGF-1 facilitates chondrocyte differentiation and maturation, thus mediating skeletal growth27,30. Enhanced insulin signaling following exercise also likely synergistically improves IGF-1 receptor signaling and optimizes energy metabolism within growth plate chondrocytes, further promoting skeletal growth31. Thus, plyometric exercise emerges as an effective clinical strategy to stimulate growth through GH-IGF-1-insulin pathway activation, even when excess adiposity persists in individuals with obesity.

Plyometric exercise has been reported to promote not only linear growth but also muscle growth through molecular regulation of myokines secreted from skeletal muscle32. Specifically, exercise-induced decreases in myostatin and increases in follistatin and IGF-1 play critical roles in enhancing muscle mass and fitness by stimulating muscle protein synthesis (MPS) and inhibiting muscle protein breakdown (MPB). Muscle mass is primarily determined by a delicate balance between MPS and MPB, tightly regulated by various myokines33. Among exercise-responsive myokines, myostatin is a representative negative regulator of muscle growth, promoting MPB and suppressing MPS by activating Smad2/3 signaling via ActRIIB receptors and inhibiting MyoD expression, thus contributing to muscle atrophy34. Conversely, follistatin serves as a positive regulator by neutralizing myostatin activity and activating the Akt1/mTORC1 signaling pathway, thereby enhancing MPS and muscle fitness35 .. IGF-1 also directly stimulates the Akt1/mTORC1 pathway, playing a central role in muscle growth by further enhancing MPS36. Consistent with these molecular mechanisms, this study demonstrated a significant decrease in myostatin levels and significant increases in follistatin and IGF-1 after the plyometric interventions. These adaptations were accompanied by moderate to large effect sizes (Cohen’s d = MPE − 0.73, FPE − 0.48 for myostatin, MPE 1.10 for follistatin, and MPE 0.51, FPE 0.54 for IGF-1), indicating robust anabolic signaling activation. The marked follistatin increase and myostatin suppression suggest enhanced muscle protein synthesis efficiency, while elevated IGF-1 further amplified MPS through Akt/mTORC1 signaling, collectively promoting muscle hypertrophy and functional gain. These myokine adaptations corresponded with small to large improvements in muscle fitness indicators, grip strength, knee peak torque, and knee muscle power (MPE 0.54 to 1.17, FPE 0.26 to 0.45). Interestingly, these functional gains were more pronounced in males, which may be attributed to the greater anabolic myokine response observed in this group. Specifically, males showed a moderated increase in muscle mass (d = 0.27) compared with minimal change in females (d = 0.02), a larger reduction in myostatin (d= -0.73 vs. -0.48), and a marked rise in follistatin (d = 1.10, not significant in females). These differences suggest that male participants experienced stronger activation of anabolic signaling pathways and greater suppression of catabolic signaling, resulting in superior improvements in muscle strength and power. In contrast, the relatively attenuated myokine response in females may reflect hormonal modulation, such as estrogen-mediated feedback on muscle protein turnover that partially limits the magnitude of hypertrophic adaptation. The integrated response across the myostatin-follistatin-IGF-1 axis strongly supports a synergistic mechanism in which suppression of catabolic signaling and activation of anabolic pathways jointly enhance muscle function. Our findings provide substantial evidence supporting the myokine-mediated regulatory mechanism centered on suppression of myostatin and activation of follistatin and IGF-1 as the key pathway simultaneously promoting muscle mass and fitness improvements. This aligns with previous studies demonstrating that adolescent plyometric exercise induces favorable myokine shifts, reinforcing the potential of plyometric training as a clinically meaningful non-pharmacological intervention for improving muscle health and functional performance in adolescents with obesity37.

Leptin and adiponectin, representative adipokines secreted by adipose tissue, critically regulate energy homeostasis, metabolism, and inflammation. Specifically, leptin primarily regulates appetite suppression and energy expenditure, whereas adiponectin exhibits anti-inflammatory effects, improves insulin sensitivity, and enhances skeletal muscle metabolic function38. In this study, leptin levels significantly decreased (MPE − 1.86, PME − 1.93) and adiponectin levels significantly decreased (both 0.68), indicating large to moderate effect sizes and demonstrating complex physiological adaptations closely linked with improved GH-IGF-1 axis and myokine activity. Hyperleptinemia typically inhibits GH secretion and IGF-1 synthesis via SOCS3 and PTP1B-mediated leptin signaling suppression39. Thus, the marked reduction in leptin observed reflects improved leptin sensitivity resulting from body fat reduction, enhancing GH-IGF-1 axis activity and restoring normal endocrine feedback. This improvement likely contributed to increased GH receptor responsiveness and facilitated IGF-1 synthesis, consistent with the previously described somatotropic adaptations. Moreover, the increase in adiponectin (both 0.68) may have further promoted skeletal muscle metabolic remodeling through AMPK and PPARα activation, optimizing mitochondrial function and energy utilization. Adiponectin also stimulates IGF-1 synthesis and suppresses myostatin expression, thereby enhancing Akt/mTORC1 signaling and synergistically supporting muscle hypertrophy and metabolic health40. The concurrent increase in adiponectin, IGF-1, and follistatin, along with a reduction in myostatin and leptin, provides compelling evidence of integrative endocrine-metabolic cross-talk. These adaptations extend beyond simple changes in body composition, encompassing systemic improvements in growth promotion, muscle function, and metabolic regulation.

However, unlike leptin and adiponectin, TNF-α showed no significant changes post-intervention. This may reflect the fact that participants remained within the clinical classification of obesity (≥ 30% body fat), suggesting that TNF-α expression is more intricately regulated by complex inflammatory pathways (e.g., TLR4–MyD88–NF-κB, JNK, MAPK) rather than moderate fat reduction alone41. TNF-α promotes insulin resistance by increasing IRS-1 serine phosphorylation and inhibiting adiponectin synthesis, and thus, significant improvement in TNF-α levels may require more substantial visceral fat loss or longer-term, multifaceted interventions involving suppression of macrophage infiltration and modulation of gut microbiota42. Our results are consistent with a previous pediatric study showing no significant changes in TNF-α following 12 weeks of moderate to high intensity exercise in childhood and adolescents with obesity43. Therefore, our findings suggest TNF-α modulation may occur at advanced stages of metabolic improvement. These results contrast significantly with previous animal studies and human research. Although animal studies have reported beneficial effects of regular exercise on alleviating leptin resistance and promoting GH-IGF-1 and adiponectin activity44, these rodent models cannot entirely reflect the physiological characteristics of human adolescents. Additionally, previous human clinical studies often analyzed limited markers such as leptin or adiponectin individually19, lacking a comprehensive integrative analysis of multiple metabolic pathways including, GH, IGF-1, TNF-α, and myokines45.

Despite these promising findings, this study has several limitations. First, although participants were stratified by chronological age, pubertal development was not directly assessed using Tanner staging or hormone profiling, which limits the precision of growth-related interpretations. Second, participants were recruited from a specific age and clinical phenotype (obesity with leptin resistance), which may restrict the generalizability of findings to broader pediatric populations. Lastly, outcome measures were assessed only at pre- and post-intervention time points, making it difficult to track the temporal trajectory of changes. Future studies should consider combining plyometric and aerobic training, incorporating pubertal hormone assessments, and conducting longer-term follow-up to evaluate the durability and scalability of these findings across diverse settings.

Conclusion

This study demonstrates that plyometric exercise is an effective intervention for improving both growth and muscle function in adolescents with obesity and leptin resistance. The 12-week program enhanced height and reduced body fat by activating the GH-IGF-1 axis and improving leptin sensitivity. In addition, decreased myostatin and increased follistatin and IGF-1 promoted muscle protein synthesis and improved muscle mass, strength, and power. These integrative adaptations, encompassing myokines, adipokines, and growth and appetite-related hormones, underscore the systemic benefits of plyometric training. Plyometric exercise can therefore serve as a safe, practical, and non-pharmacological approach to enhance growth and metabolic health in adolescents with obesity. However, as this study was limited by its 12-week duration and lack of dietary control, future long-term and multi-factorial studies are warranted to confirm these findings and elucidate the underlying mechanisms more precisely.