The Effects of Interval Resistance—Aerobic Training and Fisetin Supplementation on Asprosin and Selected Adipokines in Obese Men: A Double-Blind Randomized Control Trial

Objective: This double-blind, parallel-group randomized controlled trial is the first to investigate the synergistic effects of interval resistance plus progressive aerobic training with fisetin supplementation on adipokines in obesity. Methods: Sixty sedentary men with obesity (BMI < 30 kg/m²) completed 12 weeks of thrice-weekly interval resistance training (eight exercises, 3 × 13 reps at 60% 1RM with 20% 1RM active rest), immediately followed by staged aerobic bouts (50–70% HRmax). Participants were randomized into the control-placebo (P), fisetin (F; 200 mg/day), training-placebo (TP), or training + fisetin (TF) groups. The primary outcomes were asprosin, MCP-1, and adiponectin; secondary outcomes included leptin and lipid profile. Data were analyzed via ANCOVA with Bonferroni post hoc tests. Results: Statistical analyses were conducted following the intention-to-treat (ITT) principle using an analysis of covariance (ANCOVA) model, which revealed extensive effects of the interventions on the participants’ anthropometric and biochemical indices. Regarding body composition, after adjusting for baseline values, a significant difference in mean body weight was observed between groups (F (3, 55) = 9.444, p < 0.001, ηp² = 0.340); Bonferroni post hoc tests confirmed that the training plus fisetin (TF), training-placebo (TP), and fisetin (F) groups all achieved significant weight loss compared to the placebo (P) group. Furthermore, body mass index (BMI) showed a significant inter-group difference (p = 0.021), with post hoc analysis revealing that only the TF group reached a statistically significant reduction compared to the placebo (p = 0.024; 95% CI [−3.760, −0.172]). In the assessment of biochemical and inflammatory variables, the interventions exerted a highly significant effect on asprosin (F (3, 55) = 36.047, p < 0.001; ηp² = 0.663) and MCP-1 (F (3, 55) = 29.570, p < 0.001; ηp² = 0.617). The findings indicated that the TF group experienced the most substantial reductions in both asprosin (−60.71%) and MCP-1 (−46.50%) levels. Regarding adipokines, significant increases in adiponectin levels were observed in the TP (29.38%) and TF (27.67%) groups (p < 0.05), whereas changes in leptin were statistically significant only in the TF group relative to the placebo (p = 0.049). The lipid profile results indicated a statistically significant difference in the TF group in improving all markers; this group achieved greater reduction compared to other groups, including reductions in LDL-C, triglycerides (TG), and total cholesterol (TC) (p < 0.001), while simultaneously showing a significant elevation in HDL-C. Post hoc analyses confirmed robust statistical differences in all lipid parameters for both the TF and TP groups compared to the placebo group (p < 0.05), whereas the placebo group experienced a deterioration in status characterized by a significant increase in LDL-C (p = 0.027) and a significant decline in HDL-C concentrations (p = 0.006). Conclusions: In conclusion, 12 weeks of combined interval resistance–aerobic training and fisetin supplementation significantly reduced pro-inflammatory adipokines and improved lipid profiles in obese men. These findings suggest that asprosin serves as a potential modulator in metabolic risk reduction; however, since direct mechanistic assays were not conducted, these implications remain hypothetical. Future research employing molecular readouts is warranted to confirm the underlying pathways involved.