Journal of Exercise & Organ Cross Talk

Abstract Melanoma is an aggressive malignancy with a high propensity for metastasis, particularly to the liver. This study investigated the individual and combined effects of resistance training (RT) and pineapple extract (PE) supplementation on primary melanoma tumor growth and the expression of hepatic apoptotic markers (Bax, Bcl-2) in a murine model. C57BL/6 mice bearing subcutaneous B16F10 melanoma tumors were allocated to four groups: Tumor Control (TC), RT, PE, and Combined (RT+PE). The six-week intervention consisted of ladder-climbing RT and/or oral PE supplementation. Tumor volume was measured throughout the study. Upon completion, hepatic Bax and Bcl-2 gene expression was analyzed via qPCR. While RT and PE alone did not significantly affect tumor volume, the Combined (RT+PE) group showed a significant reduction compared to the TC group (p<0.05). In the liver, all intervention groups (RT, PE, and Combined) significantly decreased pro-apoptotic Bax expression and increased anti-apoptotic Bcl-2 expression relative to the TC group (p<0.05). The combination of resistance training and pineapple extract exhibits a synergistic effect in reducing primary melanoma tumor growth. Furthermore, both interventions independently and collectively modulate systemic apoptotic markers in the liver, suggesting a potential role in influencing the hepatic microenvironment. This non-invasive combinatorial approach may represent a promising complementary strategy for managing melanoma progression and its systemic effects.

Abstract Sciatic nerve injury results in significant functional impairment and is associated with neuroinflammatory responses. While lithium and exercise have shown independent neuroprotective potential, their combined effects remain less explored. This study investigated the therapeutic efficacy of lithium, resistance training, and their combination on functional recovery and neuroinflammatory markers in a rat model of sciatic nerve injury. Twenty-five rats were randomly divided into five groups: Sham, Model (sciatic nerve injury), Model+Lithium, Model+Resistance training, and Model+Lithium+Resistance training. Lithium carbonate (10 mg/kg, i.p.) was administered for 5 days, and resistance training was conducted for 6 weeks, with both interventions starting 24 hours’ post-injury. Functional recovery was assessed using the beam walk test. Neuroinflammation was evaluated by measuring the activity of myeloperoxidase (MPO) and nitric oxide (NO) in the cerebrospinal fluid at the end of the 6-week intervention period. Sciatic nerve injury (Model group) induced a significant deficit in beam test performance compared to the Sham group (p < 0.001). All treatment groups (Lithium, Resistance training, and Combined) showed significant improvement in functional scores compared to the Model group, with the Combined treatment group showing significantly greater recovery than either monotherapy (p < 0.05). Furthermore, the Model group exhibited a significant increase in MPO and NO levels. Resistance training alone and in combination with lithium significantly attenuated this increase (p < 0.0001). Interestingly, lithium monotherapy did not reduce the elevated neuroinflammatory markers. Our findings demonstrate that resistance training alone effectively reduces neuroinflammation and improves functional recovery after sciatic nerve injury. The combination of lithium and resistance training yields a synergistic effect, resulting in the most significant functional improvement, suggesting a promising combined therapeutic strategy for peripheral nerve injury.

Abstract The integration of herbal supplementation with exercise training may offer a novel hybrid strategy that bridges traditional medicine and modern performance science to enhance recovery and physical outcomes. This study aimed to evaluate the synergistic effects of cinnamon supplementation and Tabata-style high-intensity interval training (HIIT) on metabolic and performance outcomes in young male military cadets. Forty-eight healthy cadets were randomly assigned to four groups: Tabata training (T), cinnamon supplementation (S), Tabata + cinnamon (TS), and control (C). The intervention lasted six weeks, consisting of thrice-weekly Tabata sessions (87–100% HRmax) and daily oral cinnamon supplementation (1.5 g/day). Assessments conducted before and after the intervention included body composition, VO₂max, post-exercise blood lactate levels, and combat readiness scores based on the Army Combat Fitness Test. Statistical analysis employed paired t-tests and ANCOVA at a significance level of p < 0.05. Significant improvements were observed in the TS group compared to control: VO2max increased (p = 0.001), post-exercise lactate decreased (−1.93 mmol/L, p = 0.001), and combat readiness scores improved substantially (+63.6 points, p = 0.001). Comparable but less pronounced improvements were observed in the Tabata-only and cinnamon-only groups. No adverse effects were reported. The findings suggest that cinnamon—a time-honored medicinal spice—may potentiate the effects of high-intensity training by improving aerobic capacity, lactate clearance, and combat readiness. This study provides translational evidence supporting cinnamon as a safe, natural, and affordable traditional functional food that can enhance physical performance and metabolic resilience in tactical populations. The integration of traditional herbal supplementation with modern training paradigms offers a promising avenue in the evolving field of evidence-based traditional medicine.

Abstract Aerobic exercise has been proposed as a non-pharmacological intervention to modulate inflammatory gene expression, yet the molecular mechanisms remain incompletely understood. This study investigated the effects of a 12-week moderate-intensity aerobic exercise intervention on the mRNA expression levels of inflammation-related genes (TNF-α, IL-6, and IL-10) in peripheral blood mononuclear cells (PBMCs) of overweight individuals. Forty-five overweight adults (BMI 25-29.9 kg/m²) were randomly assigned to either an aerobic exercise group (n=30) or a sedentary control group (n=15). The exercise protocol consisted of supervised moderate-intensity aerobic training (60-75% HRmax) for 45-60 minutes, 5 days per week for 12 weeks. Blood samples were collected pre- and post- intervention for gene expression analysis using quantitative real-time PCR and protein quantification via ELISA. Following the 12-week intervention, the exercise group demonstrated significant reductions in TNF-α mRNA expression (−52.3%, p<0.001) and IL-6 expression (−47.8%, p<0.001) compared to baseline. Conversely, IL-10 expression increased significantly (+68.4%, p<0.001). Plasma protein concentrations paralleled these changes, with TNF-α decreasing from 8.6±2.1 to 4.9±1.3 pg/mL (p<0.001), IL-6 from 5.8±1.7 to 3.2±0.9 pg/mL (p<0.001), and IL-10 increasing from 3.1±0.8 to 5.6±1.2 pg/mL (p<0.001). Body mass index decreased significantly in the exercise group (−2.3 kg/m², p<0.001) with concurrent improvements in cardiorespiratory fitness (VO₂max increased by 18.7%, p<0.001). Moderate-intensity aerobic exercise effectively modulates the inflammatory gene expression profile in overweight individuals by downregulating pro-inflammatory genes (TNF-α and IL-6) and upregulating the anti- inflammatory gene (IL-10). These molecular adaptations may contribute to reduced inflammation and improved metabolic health in this population.

Abstract Crosstalk between muscle and adipose tissue via myokines and adipokines has critical implications for the metabolic regulation of type 2 diabetes. Irisin and adipolin are key secretory proteins involved in glucose homeostasis and anti-inflammatory pathways, yet the combined impact of pharmacological and physical interventions on their metabolism remains insufficiently characterized. This experimental study investigated the effects of metformin therapy and structured exercise on serum levels of irisin and adipolin, as well as related metabolic parameters, in male diabetic rats. Type 2 diabetes was induced in male Wistar rats (fasting glucose >250 mg/dl), while the healthy control group maintained normal glucose levels (~95 mg/dl). Animals were randomly assigned to control, metformin, or exercise (combined aerobic and resistance training) groups. Over eight weeks, interventions were administered and serum irisin, adipolin, and fasting blood glucose were measured pre- and post-intervention. Data were analyzed using the Shapiro–Wilk test, ANOVA, and Tukey post hoc tests. Results showed that both metformin and exercise significantly increased adipolin levels (p<0.01). As expected, irisin levels were higher in the non-diabetic control group compared to diabetic groups (p<0.05), consistent with the known reduction of irisin in diabetes. Fasting glucose improved most notably in the exercise group. These findings indicate that metformin and exercise exert distinct yet complementary effects on key metabolic regulators—adipolin and irisin—highlighting the benefits of integrating pharmacological and lifestyle approaches in type 2 diabetes management. Future research should explore underlying molecular mechanisms and translational potential in human populations.

Abstract Rapid industrial expansion in Sirjan has reshaped occupational routines in ways that constrain daily movement and heighten metabolic vulnerability. While the health benefits of physical activity are well established, this narrative review advances the argument that the more fundamental deficit in such environments is the erosion of movement literacy—the cognitive, physiological, and behavioral capacity to understand, interpret, and intentionally engage in health sustaining physical activity. Drawing on evidence from exercise physiology, metabolic science, and occupational health, we conceptualize movement literacy as a multidimensional construct comprising awareness of exercise induced mechanisms, interpretation of bodily cues, and the ability to apply this knowledge to everyday behavior. Using the Gol Gohar industrial community as an illustrative case, we describe how limited literacy in these domains contributes to sedentary patterns among workers and outline how the Gol Gohar Sports Club operationalizes a literacy oriented model through targeted public education initiatives, coach led instructional programs, and awareness based practices such as “smart running.” By synthesizing mechanistic pathways—including glucose regulation, inflammatory modulation, neuroendocrine adaptation, and myokine signaling—the review positions movement literacy as a missing but necessary dimension in industrial health policy. We argue that enhancing this form of literacy may serve as a scalable strategy to mitigate metabolic risk and integrate exercise knowledge into routine occupational life.

Abstract Irisin, a myokine cleaved from the membrane protein Fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a critical exercise-induced hormone. It is implicated in the browning of white adipose tissue, enhanced metabolic rate, and potential anabolic processes. In bodybuilding, where precise manipulation of training variables—specifically repetitions (reps) and sets—is paramount, understanding how these variables influence irisin secretion could optimize both physique and health outcomes. This narrative review aims to synthesize current evidence on the effects of resistance training protocols, with a focus on reps and sets, on irisin secretion. Furthermore, it explores the potential subsequent benefits of elevated irisin levels for bodybuilders, including its putative roles in fat metabolism, muscle remodeling, and overall metabolic health. Evidence suggests that high-volume resistance training protocols, characterized by multiple sets (≥3) and moderate repetitions (8-12 reps), may be potent stimulators of irisin release. This secretion is hypothesized to be mediated by muscle contraction-induced PGC-1α expression. Elevated irisin levels are often correlated with improved lipid oxidation, which could aid in cutting phases by promoting a leaner physique. Additionally, preclinical and some human studies suggest irisin may support muscle hypertrophy through enhanced nutrient partitioning and autocrine/paracrine signaling, though this mechanism requires further elucidation. Strategic manipulation of resistance training volume and intensity may represent a viable method for modulating irisin secretion. Incorporating protocols that could elevate this myokine might provide bodybuilders with a dual advantage: enhancing metabolic efficiency to reduce adipose tissue and potentially supporting muscle growth and recovery. However, the current evidence is not yet definitive, and more research is needed to confirm these links.

Abstract Dear Editor-in-Chief
While the systemic benefits of exercise are undeniable, the precise language of inter-organ communication remains a "black box." Recent advances suggest we are poised to decode this language, transitioning from a model of diffuse hormonal signaling to one of targeted vesicular trafficking and epigenetic reprogramming. This letter posits that the next frontier for the Journal of Exercise & Organ Cross Talk lies in elucidating the rules of cargo loading, addressing, and delivery within exercise-induced extracellular vesicles‒a process likely fundamental to the remarkable specificity of organ crosstalk.
This topic moves beyond cataloguing exerkines to interrogate the mechanisms of their targeted delivery and organ-specific effects. The most compelling frontier is understanding how exercise governs the packaging, release, and uptake of extracellular vesicles, including exosomes, which function as discrete signaling packets between organs. This intersects powerfully with metabolomics and epigenetics, bearing profound implications for metabolic disease, cancer, and neurodegeneration.
First, the paradigm is shifting from humoral to vesicular signaling. The field is moving beyond viewing exerkines as freely circulating factors to recognizing their active encapsulation into extracellular vesicles (EVs). These vesicles protect their cargo, enable tissue tropism (e.g., liver-derived EVs homing to adipose tissue or brain), and deliver diverse cargo‒proteins, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and metabolites. This mechanism explains specificity in organ crosstalk previously attributed to stochastic distribution (Vechetti Jr et al., 2021).
Second, regarding the "exercise metabolome" and organ reprogramming, focus has turned to exercise-induced metabolites (e.g, lactate, succinate) which serve as potent signaling molecules. A cutting-edge perspective is how these metabolites act as histone modifiers (e.g., via lactylation) in remote organs, directly altering gene expression in the liver, brain, and immune system to mediate long-term adaptive crosstalk (Xiao et al., 2025).
Third, the gut-muscle-brain axis represents a critical microbiome-mediated highway. Exercise modulates gut microbiota composition, which subsequently produces metabolites (e.g., short-chain fatty acids (SCFAs), bile acids) that signal to both muscle, enhancing anabolic processes, and brain, modulating neurogenesis and brain-derived neurotrophic factor (BDNF) expression. This tripartite axis is a major, yet underexplored, vector in systemic communication (Frampton et al., 2020; Liu et al., 2025).
Looking forward, the concept of personalized exerkine signatures presents a translational goal. Given individual variability in exerkine response, can we define an individual's "exerkine signature" to predict their metabolic or neuroprotective gains from exercise? This links the mechanistic basis of crosstalk directly to precision medicine.
We therefore urge the research community to prioritize the following key questions:
1. What are the exercise-intensity- and modality-dependent "sorting signals" that dictate cargo loading into EVs from distinct tissues?
2. How do tissue-specific EV uptake mechanisms confer selectivity to the remote effects of exercise?
3. To what extent do chronic exercise patterns establish organ-specific epigenetic "memories" via persistent metabolite signaling?
By leveraging single-vesicle analyses, spatially resolved metabolomics, and cell-type-specific models, we can advance from observing crosstalk to understanding its precise syntax. Decoding this language will not only illuminate fundamental physiology but also pave the way for rationally designed, organ-specific "exercise mimetic" therapies.