Journal of Exercise & Organ Cross Talk

Abstract High-intensity training is recognized as a time-efficient method for simultaneously improving physical fitness and metabolic health, but direct comparisons between high-intensity functional training (HIFT) and high-intensity multimodal training (HIMT) are limited, especially in military officer cadets. The aim of the present study was to compare the effects of high-intensity functional and multimodal training on physical fitness and cardiometabolic adaptations in military officer cadets. In this two-arm interventional study with a pre-test/post-test design and no non-exercise control group, 28 male students of Imam Ali (AS) University were randomly allocated to two groups of 14 each (HIFT and HIMT) and trained for eight weeks. Lipid profile (TC, LDL, HDL, and TG), cardiorespiratory fitness (VO2max), power (Sargent jump), and agility (Illinois Agility Test) were measured before and after the course. Data were analyzed using a mixed ANOVA at a significance level of 0.05. The main effect of time was significant for most variables; in both groups, VO2max, power, and agility improved and total cholesterol (TC) and triglyceride (TG) decreased while HDL increased (p < 0.001). LDL changes, despite a decreasing trend, did not reach significance (p = 0.071). No significant group × time interaction was found for any variable, indicating no significant differences between the two methods. Both HIFT and HIMT were associated with improvements in the physical fitness and lipid profile of military students to a similar extent over eight weeks. Therefore, either method can be used as an effective and time-efficient strategy for improving combat readiness and metabolic health, based on available facilities and conditions.

Abstract Type 1 diabetes is the most common non-communicable disease among children. This disease is associated with a lack of insulin secretion and imposes many complications on the affected person throughout his life. Sports activity can play a significant role in controlling this disease and reducing its complications. Therefore, the aim of this study is to investigate the effect of eight weeks of HOME-HIIT on glycemic control indicators in children with type 1 diabetes. In this semi-experimental study, 30 children with type 1 diabetes with an average age of 11.5 ± 2.17 and a body mass index of 19 ± 2.96 were randomly divided into two control groups (15 people) and an exercise group (15 people). The training program consisted of eight weeks and three HIIT training sessions every week with an intensity of 80-90% of the maximum heart rate. Blood samples were collected in fasting conditions in the pre-test and post-test phases or daily to investigate the studied variables. Independent T-test was used to analyze data and examine results of intragroup differences, and Bonferroni's post hoc test and dependent T-test with a significance level of (P=0.05) were used to examine intragroup differences. These cases were done using SPSS version 25 software with a p-value <0.05.The results of this research showed that HOME-HIIT has a positive effect on the indicators of glycemic control in children with type 1 diabetes, and as a result, it can help reduce the complications of diabetes and improve the health of children with type 1 diabetes.

Abstract Western diet (WD) consumption promotes oxidative stress and inflammation and plays a central role in the development of fatty liver disease. This study investigated the effects of high-intensity interval training (HIIT), ketone ester supplementation, and their combination on hepatic Keap1, Nrf2, and NF-κB protein levels in WD-fed mice. Thirty male C57BL/6J mice were randomly assigned to five groups (n=6): normal diet (ND), WD, WD plus ketone ester (WD+KE), WD plus HIIT (WD+HIIT), and WD plus HIIT combined with ketone ester supplementation (WD+HIIT+KE). Except for the ND group, all animals consumed a WD for eight weeks. HIIT was performed for four weeks (three sessions/week), and ketone ester was administered daily by oral gavage. Hepatic protein levels of Keap1, Nrf2, and NF-κB were determined using Western blotting. WD feeding significantly increased hepatic Keap1 and NF-κB protein levels and reduced Nrf2 levels compared with the ND group. HIIT and ketone ester, both independently and in combination, significantly decreased NF-κB and increased Nrf2 protein levels compared with the WD group. In addition, HIIT alone and in combination with ketone ester supplementation significantly reduced hepatic Keap1 levels (p<0.05). Overall, both interventions alleviated WD-induced alterations in hepatic oxidative stress and inflammatory signaling. The combined intervention elicited the most pronounced molecular responses, suggesting potential synergistic effects of HIIT and ketone ester supplementation in attenuating Western diet-induced oxidative stress and inflammation.

Abstract Sedentary obesity is associated with chronic inflammation, oxidative stress, and impaired angiogenesis, leading to endothelial dysfunction. Interval training and CoQ10 each improve redox balance and vascular health, possibly via inter-organ crosstalk, but their combined effects in sedentary obese men are unclear. Sixty sedentary obese men (30–45 years) were randomized into four groups (n=15): control, CoQ10 (100 mg/day), moderate-intensity intermittent training (3×/week, 8 weeks), and training + CoQ10. Serum VEGF, TAC, and H₂O₂ were measured pre/post-n via ELISA and colorimetric assays. Data were analyzed with repeated-measures ANOVA (α=0.05). Effect sizes (partial η²) were reported. Training significantly raised VEGF (p < 0.001, η² = 0.363) and TAC (p < 0.001, η² = 0.290), while strongly reducing H₂O₂ (p < 0.001, η² = 0.520). CoQ10 showed no significant main or interactive effects on TAC or H₂O₂; however, a significant three-way interaction (time × exercise × supplement) was observed for VEGF (p = 0.001, η² = 0.187). Post-hoc analysis revealed that the exercise-only group showed a greater increase in VEGF compared to the combined group, though the direct comparison between TR and TR+SUP at post-intervention did not reach statistical significance (p > 0.05). Eight weeks of interval training robustly improves VEGF and redox homeostasis in sedentary obese men, possibly through myokines/exerkines enhancing muscle–adipose–endothelial crosstalk and HIF-1α/VEGF signaling. CoQ10 provides no added benefit for most outcomes and may be associated with a modest attenuation of the exercise-induced VEGF response.

Abstract This study aimed to investigate the effects of eight weeks of resistance training (Ex), vitamin D supplementation (VD), and their combination (VD+Ex) on insulin resistance (HOMA IR), glycemic control (HbA1c, fasting glucose), inflammatory markers (interleukin 6 [IL 6] and C reactive protein [CRP]), and anthropometric measures in men with T2DM. In this single blind randomized controlled trial, 40 men with T2DM (aged 40–55 years) were randomly allocated into four groups (n=10 each): placebo control (PI), vitamin D supplementation (2000 IU/day, VD), resistance training (three sessions/week, 60–70% of 1RM, progressive overload, Ex), and combined VD+Ex. All participants maintained their usual diet, lifestyle, and anti-diabetic medications. Fasting blood samples were collected pre and post intervention to measure serum glucose, insulin, 25 hydroxy vitamin D, IL 6, and CRP. HOMA IR was calculated. Post hoc analysis showed that the Ex group had significantly lower HOMA IR than the placebo group (p=0.002), and the VD+Ex group had significantly lower HOMA IR compared to both placebo (p<0.001) and VD alone (p=0.001). The comparison between VD+Ex and Ex was not statistically significant (p>0.05). No significant difference in HbA1c was observed (p=0.210). For body fat percentage, both Ex (p=0.043) and VD+Ex (p<0.001 vs. placebo;p=0.009 vs. VD) showed significant reductions. IL 6 levels were significantly lower in the Ex and VD+Ex groups compared to placebo and VD groups (p<0.001 for both). No significant changes were found in CRP levels (p=0.078). The combination of resistance training and vitamin D did not provide additional statistically significant benefits over resistance training alone for any outcome, including HOMA IR, body fat percentage, or IL 6.

Abstract Incretin–based therapies promote weight loss primarily through appetite suppression, delayed gastric emptying, and improvements in glycemic regulation, resulting in rapid and clinically meaningful reductions in body mass. In contrast, protein-focused interventions support fat loss through enhanced satiety, preservation of diet-induced thermogenesis, and direct stimulation of muscle protein synthesis, typically producing slower but more metabolically stable changes in body composition. For physically active individuals, the interaction between these strategies and exercise introduces additional physiological considerations beyond total weight loss. Exercise, particularly resistance training, increases the demand for adequate substrate availability to support skeletal muscle maintenance, remodeling, and functional adaptation. Within this context, incretin–based therapies, induced reductions in energy intake may challenge lean mass preservation if not carefully managed, whereas protein-based strategies may align more naturally with the anabolic and recovery requirements of training. Importantly, these approaches also differ in the temporal pattern of fat loss, the extent to which lean mass is affected, and the durability of weight loss once active intervention slows or ceases, factors that are especially relevant for individuals pursuing long-term exercise adherence and performance. This review synthesizes current evidence on incretin–based therapies and protein-based dietary strategies through an exercise-relevant lens, focusing on three underexamined determinants: skeletal muscle preservation, pace of fat loss, and weight-loss maintenance. Rather than positioning these approaches as competing or hierarchical, the review aims to clarify what physiological trajectories individuals may encounter when integrating each strategy with exercise. Understanding these trajectories may help practitioners and physically active individuals make more informed, context-specific decisions when selecting fat-loss interventions.

Abstract Obesity is associated with chronic low-grade inflammation and elevated oxidative stress. This study investigated the independent and combined effects of an 8-week aerobic interval-style continuous training program and CoQ10 supplementation on serum TGF-β and MDA concentrations in inactive obese men. Sixty inactive obese men (aged 30–45 years) were randomly assigned to four groups (n=15 each): control (CONT), CoQ10 supplementation (SUP; 100 mg/day), training (TR), and combined training + supplementation (TR+SUP). The supervised training protocol was performed three sessions per week for 8 weeks with progressive intensity. Fasting venous blood samples were collected before and after the intervention. Serum MDA was measured using colorimetric assay, and TGF-β was quantified via ELISA. Data was analyzed using two-way repeated-measures ANOVA. Significant time × exercise interactions were observed for both MDA (F(1,56) = 28.793, p < 0.001) and TGF-β (F(1,56) = 30.617, p < 0.001), with reductions in the exercise groups (MDA: exercise groups from 210 nmol/L to 156 nmol/L; TGF-β: from 35 nmol/L to 30 pg/mL). Time × supplementation interactions were also significant but smaller (MDA: η_p² = 0.082; TGF-β: η_p² = 0.068). No significant three-way interaction was detected for either marker. These findings highlight aerobic interval-style continuous training as a cornerstone intervention for mitigating obesity-related oxidative stress and fibrotic signaling. CoQ10 supplementation produced a small independent reduction in both markers, but no synergistic or additive interaction with exercise was observed.

Abstract Dear Editor-in-Chief
What if the therapeutic benefits of exercise could be captured, concentrated, and delivered as a targeted molecular dose? New research on exercise-induced extracellular vesicles (ExEVs) suggests that this concept is evolving from a metaphorical understanding to a mechanistic one. Extracellular vesicles (EVs), particularly exosomes, are increasingly recognized as important facilitators of the signals generated by exercise, known as exerkines. These vesicles carry well-known myokines like IL-6 and irisin, as well as a wide range of other components, including microRNAs (miRNAs), mitochondrial DNA (mtDNA), and metabolites. This cargo is transported to distant organs, enhancing communication between muscles and various systems, including the brain, liver, and cardiovascular system (Magliulo et al., 2022; Nederveen et al., 2021).
Both aerobic and resistance training lead to a substantial increase in the secretion of extracellular vesicles (EVs) from skeletal muscle tissue, as well as a modification of their miRNA profiles, including miR-181a-5p, miR-486-5p, and miR-342-5p. These miRNAs are correlated with enhanced insulin sensitivity, reduced systemic inflammation, and neuronal protection. Consequently, this evidence underscores the role of EVs as stable carriers of exerkines that are less susceptible to enzymatic degradation and capable of delivering them more precisely than free myokines (Li et al., 2026; Silvestri et al., 2026; Wang et al., 2026).
One of the most compelling pieces of translational evidence comes from animal studies. When extracellular vesicles (ExEVs) from trained mice are injected into models of muscle disuse, they effectively preserve muscle mass and enhance regeneration (Fliflet et al., 2026). This serves as a strong proof-of-concept for developing exercise- mimetic therapeutics that can work without the need for actual exercise. In human studies, the profiles of extracellular vesicles following exercise are similarly associated with improved metabolic function and decreased markers of biological aging (Plaza-Florido et al., 2024).
Ongoing methodological obstacles, particularly in the standardization of extracellular vesicle (EV) isolation techniques, such as ultracentrifugation compared to size-exclusion chromatography, as well as in the accurate identification of their sources, whether from muscle, endothelial cells, or platelets. We propose that forthcoming investigations should progress beyond these unresolved issues towards a definitive roadmap: a multi-omics profiling approach—encompassing transcriptomics, proteomics, and lipidomics—of extracellular vesicles (ExEVs) across various exercise modalities (high-intensity interval training versus endurance training), while systematically considering sex-specific responses and age-stratified cohorts ranging from adolescence to older age. This framework would establish the groundwork for the development of vesicle-based "exercise pharmacology" (Nederveen et al., 2021).
This pioneering area not only advances our understanding of the molecular underpinnings of how exercise imparts its benefits, but also establishes a groundbreaking trajectory for therapeutics centered on extracellular vesicles—exosome mimetics formulated to treat obesity, type 2 diabetes, and sarcopenia independently of physical activity. Such developments could significantly reshape the notion of exercise prescription in medical practice.
Given the substantial transformative potential of this field, we recommend that your journal launch a special issue or thematic series on "Exercise-Derived Extracellular Vesicles in Precision Medicine." This initiative would integrate mechanistic, translational, and clinical research to fortify this swiftly evolving sector and delineate its future pathways. We believe that this Letter will be of great interest to your audience and look forward to your thoughtful consideration.

Abstract Aging in women accelerates declines in anabolic hormones and disrupts lipid homeostasis, increasing cardiometabolic risk. Whether combining blood flow restriction (BFR) with functional training provides greater benefits for irisin, IGF-1, and lipid indices than functional training alone remains unclear. This study examined the effects of 8 weeks of functional training with and without BFR on these outcomes in older women. Thirty-six older women (mean age, 63.41 years) were randomly assigned to functional training with BFR (FTBFR; 20–55% 1RM), functional training (FT; 40–75% 1RM), or control (CON). The exercise protocol included 10 functional movements performed three times weekly for 8 weeks. Fasting blood samples were collected before and 48 hours after the final session. Serum irisin and IGF-1 were measured by ELISA, and lipid indices (TC, TG, LDL, and HDL) were assessed using enzymatic assays. Data were analyzed using paired t-tests and ANCOVA (P < 0.05). Significant between-group differences were observed for irisin (P = 0.0001), IGF-1 (P = 0.001), and the LDL/HDL ratio (P = 0.0001). Both training groups increased irisin (FTBFR, 32.85%; FT, 23.98%) and IGF-1 (FTBFR, 14.03%; FT, 9.28%) and reduced the LDL/HDL ratio (FTBFR, 25.09%; FT, 18.39%), whereas no changes occurred in CON. FTBFR produced a greater improvement in the LDL/HDL ratio than FT (P = 0.025). Eight weeks of functional training improved endocrine and lipid-related biomarkers in older women. Adding BFR may enhance lipid-related adaptations during low-load functional training, although its independent contribution requires further investigation.