Comparative efficacy of exercise modalities added to energy restriction on inflammatory markers in obesity: a systematic review and network meta-analysis.

Background: Chronic low-grade inflammation is a prominent feature of obesity, a major driver of cardiometabolic risk. While energy restriction (ER) is central to obesity treatment, the comparative effects of different exercise modalities added to ER on inflammatory biomarkers and insulin resistance remain unclear. Methods: We systematically searched for randomized controlled trials evaluating energy restriction (ER) alone, ER combined with aerobic exercise (ER+AE), high-intensity interval training (ER+HIIT), or combined exercise (ER+COE) in participants with overweight or obesity. The primary comparisons were ER+exercise interventions vs. ER alone. Treatment effects were quantified as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Treatment hierarchy was explored using the Surface Under the Cumulative Ranking Curve (SUCRA) and interpreted as supportive rather than primary evidence. Results: Twenty-four randomized controlled trials involving 1,694 participants were included. Compared with ER alone, ER+AE yielded relatively steady incremental improvements across inflammatory endpoints, with favorable effects on CRP (SMD -0.52, 95% CI -0.97 to -0.07), hs-CRP (SMD -0.32, 95% CI -0.52 to -0.12), TNF-α (SMD -0.48, 95% CI -0.85 to -0.11), and IL-6 (SMD -0.35, 95% CI -0.64 to -0.06). For secondary outcomes, ER+COE was associated with a greater increase in adiponectin than ER alone (SMD 0.56, 95% CI 0.07 to 1.05), although this finding should be interpreted cautiously given the smaller evidence network. By contrast, none of the exercise-combined ER interventions showed statistically significant additional improvements in HOMA-IR compared with ER alone. No statistical evidence of global or local inconsistency was detected; however, the power to detect inconsistency was limited because several outcome networks were small or sparsely connected. Conclusions: When ER alone was used as the primary comparator, adding exercise produced biomarker-specific incremental benefits. ER+AE showed noticeable additional anti-inflammatory effects, particularly for hs-CRP, CRP, TNF-α, and IL-6. ER+COE was associated with increased adiponectin, whereas no exercise modality demonstrated a statistically significant additional benefit for HOMA-IR beyond ER alone. Overall, adjunctive exercise may provide targeted immunometabolic benefits during ER-based obesity treatment, but the current evidence does not support a single universally superior exercise modality. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251175681, identifier CRD420251175681.