Journal of Exercise & Organ Cross Talk

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 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 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 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 Incretin–based therapies and protein-based dietary strategies represent two increasingly prominent approaches for fat loss in individuals with obesity, including those who engage in structured exercise. 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. 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.