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 Dear Editor-in-Chief
Overweight and obesity are considered as the most important lifestyle-related diseases today such that they are known as the fifth leading causes of death worldwide according to the published statistics. Moreover, as previous studies have shown, low-grade chronic inflammation is among the symptoms of these diseases and plays a key role in the pathogenesis of various physical problems and chronic diseases, such as cancer, diabetes, metabolic syndrome, cardiovascular, and neurodegenerative diseases (Safaei et al., 2021).
Meanwhile, new evidence suggests that leucine-rich α 2-glycoprotein 1 (LRG1) proinflammatory factor, an important upstream signaling pathway of transforming growth factor_⁃β (TGF_⁃β), will cause several pathological processes (Zou et al., 2022). In other words, it can be stated that LRG1, alone or in combination with other known factors, is considered as a potential biomarker for inflammation and obesity. There is a positive relationship between high levels of LRG1 and obesity, while low levels of plasma LRG1 predict weight loss in surgery for obesity and metabolic diseases (Pek et al., 2018). Investigation of the importance and the relationship of this issue in a broad study on 2,058 patients with type 2 diabetes showed that higher plasma LRG1 levels in women than men have a significant relationship with several risk factors for cardiovascular disease, namely arterial stiffness, endothelial dysfunction, systolic blood pressure, obesity, kidney disease, and high-sensitivity C-reactive protein (Pek et al., 2018; Zou et al., 2022). A recent 8-year longitudinal study also found that pigment epithelial-derived factor and plasma LRG1 mediated the inverse relationship between skeletal muscle mass and chronic kidney disease progression in patients with type 2 diabetes (Low et al., 2021). In other words, there is a positive correlation between high LRG1 levels in blood serum and adipose stores and high levels of body-mass-index (BMI), visceral adipose tissue, and waist circumference of obese people. According to these results and laboratory observations, LRG1 has been assumed to increase fat accumulation via suppression of fatty acids catabolism and inducing lipid biosynthesis through sterol regulatory element-binding transcription factor 1 activation or may enable hyperglycemia by decreasing expression of insulin receptor substrates (IRS1 and IRS2) (He et al., 2021).
On the other hand, consistent with the findings of studies showing the high serum levels of LRG1, it is possible that LRG1 binds preferentially to liver cells. With this assumption, LRG1 is considered a new adipokine that can play a role in obesity conditions by regulating an almost unique cross-talk between adipose tissue and the liver. More broad research is required to know whether LRG1 also exerts metabolic functions in physiological circumstances or not. However, the results of a study on LRG1 knockout mice with a high-fat diet revealed weight loss, smaller fat cell size, and preservation of brown adipose tissue in this type of mice. In other words, an increase in LRG1 gene expression during the process of fat lipogenesis can play an important role in regulating energy homeostasis (He et al., 2021; MacCannell et al., 2021). However, changing lifestyle by performing regular physical activity and a balanced diet have been introduced as a useful solution to prevent obesity. In this regard, a recent study on the elderly with an average BMI of 34 ± 1 kg / m2 showed that exercise combined with diet resulted in an 8-10 % weight loss in these individuals, indicating the possibility that molecular changes in peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) pathway can help transport fat and oxidize it in the skeletal muscles of older and obese people and in some ways regulate insulin resistance (Mulya et al., 2017).
Previous research studies have referred to the key role of PGC-1α in regulating mitochondrial function and helping regulate cellular energy status by enabling cellular energy in conditions 
when the body needs energy, such as fasting, performing exercise activities, or inhibiting it when the body has enough energy available. However, the evidence obtained regarding the role of PGC-1α and its relationship with LRG1 gene expression in obesity therapy showed that LRG1 expression in white adipose tissue reduced in mice model of insulin - resistant type II diabetes and obesity following treatment with PPARγ agonists (Muise et al., 2008). Moreover, evidence regarding the positive effects of exercise activity and the role of PGC-1α showed that probably five proteins, including interleukin 15 (IL-15), fibronectin type III domain- containing protein 5 (FNDC5), vascular endothelial growth factor B (VEGF-B), LRG1, and tissue inhibitor of metalloproteinase 4 (TIMP4), secreted in skeletal muscles, increase following endurance exercise activity and contribute to longevity as well (Boström et al., 2012).
Considering the evidence presented, LRG1 seems to play a key role in the pathogenesis of obesity. However, more broad research is required to better understand its relationship with other transcription factors, vital signaling pathways in this process, as well as the important effect of type, intensity, and duration of exercise activity, and type of diet in regulating its expression and its regulatory role in cross-talk with other organs to prevent obesity (Yang et al., 2021). 

Abstract Dear Editor-in-Chief
New approaches to endocrinology have confirmed that every cell secretes hormones. These secreted substances are called cytokines. However, they are also named based on their origin. For example, the secretions of adipose and muscle tissue cells are called adipokines and myokines, respectively (Chait & den Hartigh, 2020).
The endocrine function of adipose tissue has been determined in some studies. It secretes substances called adipokines. Released adipokines (such as leptin, adiponectin, visfatin, resistin, omentin) act as autocrine/paracrine and endocrine (Landecho et al., 2019).
 Adipokines play an essential role in regulating glucose and lipid metabolism, energy homeostasis, nutritional behavior, insulin sensitivity, inflammation, the immune system, adipose tissue production, vascular function, coagulation, and other bodily functions (Chait & den Hartigh, 2020). Leptin, for example, regulates body fat mass and obesity (when it increases in the bloodstream) through appetite and satiety receptors (in the hypothalamus). Unlike leptin, adiponectin reduces body fat mass and regulates glucose and lipid homeostasis. The resistin can be thought of as a link between obesity, diabetes, and insulin resistance. The visfatin plays an essential role in inflammatory and infectious diseases through pro-inflammatory and anti-apoptotic ability. Omentin significantly reduces the acute phase protein in endothelial cells and can be considered an anti-inflammatory adipokine (Landecho et al., 2019). In general, adipokines act as a mediator in regulating the function of tissues and other organs such as the liver, skeletal muscle, pancreas, and cardiovascular system. Adipose tissue dysfunction plays a significant role in insulin resistance, type 2 diabetes, cardiovascular disease, and metabolic disease (Balistreri, Caruso, & Candore, 2010).
Exercise promotes adaptation to skeletal muscle, adipose tissue and consequently prevents metabolic disorders. Physical activity causes these beneficial effects by altering myokines (skeletal muscle secretions) and adipokines. Adipokines and myokines play a role in facilitating tissue-to-tissue communication (tissue crosstalk) and work together to improve health. Studies show that skeletal muscle releasing myokines during a contraction may influence adipokines (Leal, Lopes, & Batista, 2018). Moreover, Shirvani et al. showed a significant positive correlation between plasma levels of irisin with the nesfatin-1 and a significant negative correlation with resistin. Therefore, physical activity could create metabolic crosstalk between skeletal muscle and adipose tissue (Shirvani & Rahmati-Ahmadabad, 2019). Doing crosstalk research by researchers is crucial to better understand the health-related molecular mechanisms (created by exercise).