Background/Objectives: This study evaluated exercise-induced changes in body composition and metabolic biomarkers in women across distinct BMI categories and individuals with Type 2 diabetes. Methods: In this quasi-experimental study, 40 sedentary women were stratified into five groups (n = 8): underweight, normal weight, overweight, obese, and T2DM. The rigorous eight-week supervised program utilized submaximal exercise at 70–85% heart rate reserve, calculated via the Karvonen method and monitored by telemetry. Assessments included anthropometric parameters (BMI, fat mass, visceral fat) and serum biomarkers (irisin, myonectin, HIF-1α, insulin, glucose). Fasting venous samples were collected at baseline and 72 h post-intervention to minimize acute effects, then analyzed using validated ELISA protocols. Statistical data were evaluated using parametric or non-parametric tests with significance set at p < 0.05. Results: Post-intervention, significant reductions in weight, fat mass, and visceral fat occurred in overweight, obese, and T2DM groups (p < 0.05). Muscle mass increased across all cohorts. Fasting insulin and glucose decreased significantly in all except the underweight group, with the most pronounced improvements in T2DM and obese participants. Serum irisin increased significantly across all groups (p < 0.05), indicating a universal exercise-induced myokine response. Conversely, myonectin levels decreased significantly only in the normal-weight group, while HIF-1α increased specifically in the T2DM cohort. These findings suggest that baseline BMI and metabolic status are critical determinants of exercise responsiveness, leading to heterogeneous biomarker patterns despite consistent improvements in body composition and basic glycemic regulation. Conclusions: An eight-week submaximal program effectively improves body composition and glycemic regulation, though specific biomarker responses are highly dependent on baseline BMI and metabolic status.

Background/Objectives: Carnosine and exercise independently improve metabolic health, yet their combined effects on myokines and microbiota-derived metabolites remain underexplored. This study evaluated the synergistic impact of carnosine supplementation and exercise intensity on microbiota-derived metabolites, as well as skeletal muscle and myocardial expression of irisin and myonectin, focusing on lipid and glycemic regulation. Methods: A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA). Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks. Blood samples were collected post-decapitation; plasma was analyzed for lipid profile, glycemic parameters, and microbiota-derived metabolites using enzymatic and ELISA methods. Irisin and myonectin levels were assessed in plasma and myocardial and skeletal muscle tissues via ELISA and immunohistochemistry. Results: The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index. Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA. The trimethylamine N-oxide (TMAO) was lowest and S-equol highest in HICT_CA, whereas indoxyl sulfate (IS) peaked in HICT and was lowest in the C group. Principal component analysis revealed strong positive associations between HICT_CA and cardiometabolic biomarkers. Conclusions: High-intensity training combined with carnosine may reduce weight gain, improve lipid and glycemic profiles, and enhance myokines and microbiota-derived metabolites.