Journal of Exercise & Organ Cross Talk

Abstract Dear Editor-in-Chief
The global epidemic of childhood obesity continues to challenge healthcare systems, with recent epidemiological data confirming a tenfold increase in prevalence over four decades. While the complications of pediatric obesity are well documented, the field of predictive medicine urgently requires reliable biomarkers that identify at-risk children before irreversible metabolic dysfunction develops. The Journal of Exercise & Organ Cross Talk has consistently highlighted the importance of inter-organ communication in metabolic health. Herein, we propose that the brain-muscle-adipose tissue triad represents a pivotal axis for developing predictive strategies in childhood obesity.
Recent evidence has substantially advanced our understanding of adipose tissue signaling in pediatric populations. A study of 104 children aged 7-18 years demonstrated that circulating spexin and adiponectin are significantly associated with insulin resistance in pediatric obesity. Notably, spexin exhibited a biphasic pattern characterized by an initial compensatory increase followed by a decompensated decrease, suggesting its potential as an early warning signal for metabolic deterioration. Adiponectin emerged as an independent determinant of HOMA-IR (β = −0.577, p = 0.005), reinforcing the central role of adipose-derived signals in systemic insulin sensitivity (Lian et al., 2026). These findings position adipokines as accessible biomarkers for stratifying risk in children with obesity.
Expanding beyond adipose tissue, large-scale proteomic analyses have revealed multi-organ signatures of cardiometabolic risk. In a cross-sectional study of 4,024 children and adolescents, Stinson and colleagues identified protein signatures linking obesity to dyslipidemia, insulin resistance, and hypertension. Using machine learning approaches, a three-protein panel (CDCP1, FGF21, HAOX1) combined with liver enzymes improved prediction of steatotic liver disease compared to enzymes alone (ROC-AUC = 0.83 vs. 0.77, p < 0.05). Importantly, reductions in adiposity during a one-year intervention were associated with decreased inflammatory cytokines, demonstrating the modifiable nature of these biomarkers (Stinson et al., 2026). This work underscores that circulating proteomic signatures reflect integrated signals from multiple organs, including liver, adipose tissue, and potentially skeletal muscle.
The central nervous system's role in this crosstalk cannot be overlooked. A comprehensive Mendelian randomization study investigating the fat-brain axis revealed bidirectional causal relationships between body fat measures and brain phenotypes. Body fat composition showed negative genetic correlations with intelligence and cognitive performance, while positive correlations emerged with attention-deficit/hyperactivity disorder, stroke, and depression. These genetic insights suggest that the brain is not merely a passive recipient of peripheral metabolic signals but actively participates in a bidirectional dialogue with adipose tissue. For predictive medicine, this implies that neurobehavioral assessments could complement biochemical markers in identifying children at greatest metabolic risk (Baranova et al., 2025).
The convergence of these findings carries translational implications. First, the identification of early biomarkers such as spexin and adiponectin enables risk stratification before frank insulin resistance develops. Second, proteomic signatures incorporating multiple organ-derived proteins offer enhanced predictive accuracy for specific outcomes like steatotic liver disease. Third, genetic evidence linking brain phenotypes to body fat measures suggests that predictive models should incorporate both biochemical and neurobehavioral parameters.
For JEOCT readers, these advances highlight opportunities for exercise-based interventions targeting inter-organ communication Physical activity potently modulates the secretome of skeletal muscle, adipose tissue, and potentially the brain. Understanding how exercise-induced signals influence the brain-muscle-adipose triad could inform personalized exercise prescriptions for children with obesity. Future research should prioritize longitudinal studies mapping the temporal dynamics of these biomarkers during childhood development and in response to lifestyle interventions.
In conclusion, the brain-muscle-adipose tissue triad represents a conceptual framework for predictive medicine in childhood obesity. By integrating adipose-derived signals, multi-organ proteomic signatures, and brain-body genetic links, we can move toward early identification of at-risk children and targeted preventive strategies. The Journal of Exercise & Organ Cross Talk is ideally positioned to advance this research agenda.
 

Abstract Unmanaged Type 2 Diabetes (DM2) is a known risk factor for cognitive decline, dementia, and Alzheimer's disease (DM3). This study explores the combined effects of high-intensity interval training (HIIT) and thyme honey on the expression of genes involved in memory-related signaling pathways (BDNF-TrkB-CREB), which are compromised in both DM2 and DM3. This experimental study involved 36 young male Wistar rats, divided into four groups: control (C), HIIT (T), thyme honey (H), and HIIT-thyme honey (TH). The T and TH groups underwent 40 training sessions over two months, with progressively increasing intervals (from 2 to 8) and intensity (from 80% to 95% of maximum running speed). Concurrently, the H and TH groups were administered 3 g/kg of thyme honey 5 days a week. Changes in BDNF, TrkB, and CREB gene expression were assessed using RT-PCR. The data were analyzed through one-way ANOVA, Bonferroni post hoc test, and Univariate analysis using SPSS-22 software. A significant increase in BDNF and CREB expression in the interactive intervention group and the expression of the TrkB gene in honey intervention groups were observed compared to diabetic control (P≥0.001). The interactive intervention with HIIT exercises and thyme honey has a synergistic effect on increasing gene expression in memory-related pathways. The highest effect size was observed for HIIT training on BDNF (EF=0.667) and CREB (EF=0.540), while the honey intervention showed a significant effect size on TrkB (EF=0.666).

Abstract Dear Editor-in-Chief
The brain weighs about 1.36 kg and is mainly composed of blood. Although the brain includes only 2% of the body's weight, it receives 25% of the whole body oxygen consumption, 15% of the cardiac output volume and 2000 L of blood flow per day (Hartmann et al., 1994; Ohta et al., 1992; Xing et al., 2017). The brain has largest and most complex structure of the central nervous system. This organ regulates the functions of human body and stands for the basis of higher neural activities such as consciousness, alertness, learning, memory, intelligence, spirit and language learning. Cognitive function in a person means the brain ability to process, store, and extract information. In addition, this ability is a kind of advanced psychological function such as thinking, memory, and attention. Cognitive function plays an irreplaceable role in our daily life and study. Based on Cognitive psychology, the brain can modify its structure and function according to environmental changes and the experience of different types of exercising, especially exercise training, plays a crucial role in the evolution of the brain (Barnes. 2015; Raichlen et al., 2017). For example, exercise can positively affect synaptic plasticity and synaptic function to promote cerebral cortex, neural network and hippocampus function (an important structure in the memory information processing) (Ding et al., 2006; Li et al., 2019; Loprinzi et al., 2017). Exercise also has a significant effect on brain metabolism. Exercise not only promotes physical health of people, but also prevents mental illness and delays cognitive aging (Robinson et al., 2018).
Brain function depends on nerve fibers, number of neurons and synapses.  The cognitive performance is also closely related to the number of nerve fibers and synaptic connections, which can be reduced by diseases and aging process. The neurotrophics factors, such as neurotrophic factor (NGF) and brain-derived neurotrophic factor (BDNF) are required to provide nutrients to maintain the structure and function of nerve fibers and synaptic connections (Ivanov, 2014). However, with aging, sharp decrease of dendritic branches, degeneration of glial cells, the reduction of neuron number and contraction of nerves may impede the transmission of electrical signals in the nervous system, leading to the shrinkage of gray matter in the brain and cognitive impairment (Reisberg et al., 2008; Thorin-Trescases et al., 2018).
Several studies have shown that an active lifestyle could delay the aging of cognitive-control areas in the brain, and exercise can significantly improve brain health in patients with Alzheimer's disease and schizophrenia (Falkai et al., 2017; Frederiksen et al., 2018). Colcombe et al. (2003; 2006) used high-resolution magnetic resonance imaging (MRI) to scan the brain of 55 healthy people aged from 55 to 79 years old and observed a decrease in tissue density in the frontal and temporal lobes with age. The important point is that brain structure atrophy was related to aerobic fitness. In another study, 59 healthy people aged from 60-79 years old were divided into exercise training groups and control group. In the exercise training group, aerobic exercise intervention was conducted for 6 months. The results showed that the volume of gray matter and white matter was significantly increased in the exercise training group, and the researchers concluded that aerobic training could effectively delay brain aging process and lead to promote brain health (Colcombe et al., 2003; Colcombe et al., 2006; Colcombe & Kramer, 2003).
In terms of the mechanism based on which exercise training may enhance cognitive ability and  delay brain aging, it has been proved that exercise training can induce fibronectin type III domain-containing protein 5 (FNDC5) expression in skeletal muscle which will be released into the circulation with Irisin variant (Wrann et al., 2013). Spiegelman found that exercise training for 30 days in mice increased the activity of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), which is a metabolic regulatory molecule in skeletal muscle. PGC-1α could stimulate the upregulation of FNDC5 expression, and when FNDC5 enters the hippocampus through the blood-brain barrier, it enhanced the expression of BDNF in the dentate nucleus of the hippocampus (responsible for learning and memory). Interestingly, the study on sedentary mice injected with FNDC5 produced by exercise showed it activated gene for the brain health and improved the growth of new neurons involved in learning and memory. This new discovery links FNDC5, PGC-1α and BDNF in the cross talk between the brain and skeletal muscle upon exercise (Wrann et al., 2013). In addition to PGC-1 α/FNDC5 signaling on other molecules have also been found to affect BDNF expression in cognitive impairment.
In a cell model simulating the effect of exercise by adding AMPK agonist to L6 myoblasts rat, proteomics and mass spectrometry were performed to screen the factors secreted by myoblasts. Data showed that Cathepsin B (CTSB) increased after treatment while other cytokines did not changed. Meanwhile, CTSB levels also increased in gastrocnemius muscle and plasma of rats after voluntary wheel running exercise, anti-fatigue ability; spatial memory ability and coordinated movement improved in the exercised rats compared to the sedentary control group. However, these beneficial effects were absent in CTSB knockout rat. In addition, intravenous injected CSTB is able to enter the brain through blood-brain barrier and upregulate DCX and BDNF expression and thus enhancing hippocampal nerve growth (Moon et al., 2016).
Aerobic Training not only promotes physical health of people, but also prevents mental illness and effectively delays brain aging process, prevents brain structure atrophy, promotes volume gray and white matter and  promotes cognitive ability in patients with Age-induced cognitive impairment. Therefore, it is very important to conduct original and cross-sectional research in order to discover relevant and new mechanisms.
 

Abstract This study aimed to investigate the interactive effect of aloe vera intake and eight weeks’ aerobic exercise on serum BDNF, glucose, and insulin levels in women with type 2 diabetes. In this experimental study, 32 women with type 2 diabetes were selected and randomly divided into four groups of control, supplement, exercise, exercise + supplement. The exercise program was performed 3 sessions per week for 8 weeks (40 min of exercise with 50-60% of heart rate reserve in the first four weeks and 60 min of exercise with 60-80% of heart rate reserve in the second four weeks). The supplement taking groups received 400 mg/kg of oral aloe Vera 3 days per week for 8 weeks. The data were analyzed using analysis of covariance (ANCOVA). A significant increase was observed in BDNF levels, insulin sensitivity of patients in the supplement, exercise, and exercise + supplement groups (p=0.001). The glucose and insulin levels, insulin resistance, BMI, and body fat percentage significantly decreased in the supplement, exercise, and exercise + supplement groups (p=0.001). It seems aloe Vera intake and aerobic exercise to have protective effects against development of type 2 diabetes complications in women.