Journal of Exercise & Organ Cross Talk

Abstract Hepatic gene expression of inflammatory and growth factors such as IL-8 and bFGF2 may be modulated in melanoma metastasis. Non-pharmacological interventions like exercise and anti-inflammatory supplements represent potential complementary strategies for modification. This study aimed to investigate the effects of aerobic exercise, pineapple extract supplementation, and their combination on the hepatic expression of CXCL2/IL-8 HOMOLOG and bFGF2 genes in a murine melanoma model. Melanoma-bearing mice were allocated into four groups (n=5 per group): Control, Aerobic Exercise, Pineapple Extract Supplement, and Aerobic Exercise+Pineapple Extract. After the intervention period, liver tissue was analyzed for CXCL2/IL-8 HOMOLOG and bFGF2 gene expression via one-way ANOVA and Tukey HSD test. Pearson correlation assessed the relationship between the two genes. A significant difference was observed in CXCL2/IL-8 HOMOLOG gene expression between groups (F=4.211, p=0.0239). Post hoc analysis revealed that only the combined Aerobic Exercise + Pineapple Extract group showed a significant decrease in hepatic CXCL2/IL-8 HOMOLOG compared to the Cancer Control group (p=0.0251). In contrast, no significant difference was found in bFGF2 gene expression across groups (F=1.425, p=0.2745). Correlation analysis indicated a significant negative relationship between CXCL2/IL-8 HOMOLOG and bFGF2 exclusively in the Cancer Control group (r=-0.948, p=0.013). The combination of aerobic exercise and pineapple extract supplementation significantly reduces hepatic CXCL2/IL-8 HOMOLOG expression in melanoma-bearing mice, suggesting a potential synergistic effect in modulating the hepatic inflammatory microenvironment. The distinct lack of effect on bFGF2 and the specific negative correlation in controls highlight pathway-selective responses.

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 In Diabetes (Di) exercise training especially high-intensity interval training (HIIT) reduce blood lipids and improve anti-inflammatory status. In this study, we aimed to investigate the impact of high-intensity interval training on ASC inflammasome, lipid profile, and their correlation in diabetic rat models. Twenty rats were divided into four groups, including a control group, HIIT, Di, and Di+HIIT (n=5 in each group). Diabetes was induced using a combination of a high-fat diet (HFD) and STZ. Wistar rats in the exercise groups were subjected to high-intensity interval training for eight weeks. After sample collection, liver tissue was removed and weighed. Serum levels of lipid profile were measured by special kit. Protein expression of the apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) in liver tissue was determined by Western blot. The results of the present study showed that diabetes induction significantly increased LDL, cholesterol, triglyceride and ASC levels and decreased HDL levels (p<0.05), whereas HIIT exercise training with diabetes somewhat adjusted the lipid profile and decreased the ASC inflammasome levels (p<0.05). In the correlation analysis, only the correlation between ASC and triglycerides was confirmed in the Di+HIIT group (p=0.043, r=0.997). Diabetes induction adversely affects lipid profiles and increases ASC inflammasome levels. However, high-intensity interval training (HIIT) appears to mitigate these effects by improving the lipid profile and reducing ASC levels. Notably, a significant positive correlation between ASC and triglycerides was observed in the diabetic rats undergoing HIIT, suggesting a link between inflammation and lipid metabolism.

Abstract The presence of tetracycline in animal products has toxic and destructive effects on body tissues. In this study we investigate the potential protective mechanism of high-intensity interval training (HIIT) against tetracycline-induced hepatic steatosis (HS) and testicular apoptosis in male Wistar rat. In this study, forty-eight male Wistar rats (8-week, 220±10 gram) were randomly divaded into six groups of primary control (pre week one), primary HS (tetracycline-induced HS), secondary control (after week five), secondary HS, (5) HIIT, and HS+HIIT (after week five). Tetracycline was administered to rats 140 mg / kg for 7 days by gavage. HIIT was performed on rodent treadmill 5 days/week for 5 weeks.  Oral exposure of tetracycline for 7 days caused severe testis damage as indicated by significant alterations in histomorphological, apoptosis, increase Bax, P53 and decease Bcl2 (gene and protein, p=0.001) compared to primary control. But the changes of PARP1 were not significant (p>0.05). However, HIIT and HS+HIIT groups significantly increased spermatogonium counts, spermatocyte cell counts & spermatid cell counts (p=0.001 for all) in line with Bcl-2 and PARP1 (gene and protein, p=0.001) and decreasing apoptotic cells, Bax and p53 compared with secondary HS group (p=0.001). This research provides the first evidence that the beneficial anti-apoptosis effects of HIIT on testis of rats poisoned with tetracycline. This beneficial effect of HIIT on hepatic steatosis and testicular damage and toxicity due to tetracycline might be mediated by inhibiting P53-induced BAX upregulation and preventing apoptosis-mediated degradation of PARP-1.

Abstract This research paper delves into the intricate interplay between the heart and liver within the realm of metabolic regulation, focusing on the impact of exercise as a pivotal modulator of this dynamic relationship. Through a comprehensive review of pertinent literature, encompassing peer-reviewed articles, reviews, and meta-analyses sourced from databases such as PubMed, Scopus, and Google Scholar, this paper analyzes the existing understanding of how exercise influences the metabolic crosstalk between the heart and liver. The findings underscore the positive influence of regular physical activity on the metabolic interplay between these vital organs, ultimately contributing to enhanced overall metabolic health. Emphasizing both physiological and molecular aspects, the review provides a succinct overview of its content, highlighting the significance of exercise in modulating metabolic processes. In exploring human studies, animal models, and molecular techniques, this review aims to not only consolidate current knowledge but also to identify research gaps, fostering a foundation for future investigations. The potential therapeutic implications of exercise in mitigating metabolic disorders through the modulation of heart-liver crosstalk are discussed. By addressing inclusion criteria such as studies published within the last decade, written in English, and focusing on human or animal models, this paper contributes to the evolving understanding of the intricate relationship between exercise, heart health, and liver function.

Abstract Steatosis is a common disease worldwide. High intensity interval training (HIIT) may ameliorate steatosis, possibly through interactions between skeletal muscle and liver; however, mechanistic pathways are poorly understood. We aimed to determine potential mechanisms involved in skeletal muscle-liver crosstalk by measuring the gene expression of skeletal muscle interlukin-18 (IL-18) and fibronectin type III domain-containing protein 5 (FNDC5) and hepatic matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9). Thirty-two adult male Wistar rats were randomly divided into four group including normal control (C), high intensity interval training (HIIT), hepatic steatosis+ HIIT (HS+HIIT) and sedentary hepatic steatosis (SHS). HIIT was performed 5 days per week for 5 weeks. Tetracycline (140 mg/kg) was administered by gavage for 7 days to induce NAFLD. We found that HIIT and HS+HIIT increased skeletal muscle expression of FNDC5 relative to SHS group but the increase was attenuated in HS+HIIT. SHS increased muscle IL-18 expression relative to HIIT, HS+HIIT, and C. Expression of hepatic MMP-2 and MMP-9 increased significantly in SHS in comparison with C. There was a significant increase in MMP-9 in HIIT compared with C. Moreover, hepatic MMP-9 expression decreased in both HIIT and SHS+HIIT relative to SHS. MMP-2 decreased significantly in HIIT compared with SHS. Furthermore, muscle IL-18 gene expression was significantly associated with gene expression of hepatic MMP-2 and MMP-9. We conclude that HIIT-induced alteration of skeletal muscle-derived myokines may alter the gene expression of hepatic matrix metalloproteinases, collagenases involved in pathogenesis of liver diseases. Furthermore, steatosis may possibly influence myokine profiles in skeletal muscle. Accordingly, skeletal muscle-liver crosstalk is possibly targeted by HIIT and steatosis in terms of therapeutic approach.