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Life sciences · Review
Peerj · November 3, 2026
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Background Overweight and obesity are common among middle-aged and older adults, and obesity is a chronic, multifactorial disease that, particularly when accompanied by central adiposity or metabolic abnormalities, is associated with increased cardiometabolic, cancer-related, musculoskeletal, and functional risks. Leptin and ghrelin are key hormones involved in energy balance regulation and may be dysregulated in obesity, but evidence regarding the effects of exercise interventions on leptin and ghrelin levels in middle-aged and older adults with overweight or obesity remains inconsistent. This review aimed to evaluate the effects of exercise interventions on leptin and ghrelin levels in this population. Methods PubMed, Web of Science, Embase, the Cochrane Library, and CNKI were searched from database inception to 5 July 2026. Eligible studies were randomized controlled trials that enrolled middle-aged or older adults with overweight or obesity and reported leptin or ghrelin levels before and after an exercise intervention. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were synthesized using Review Manager 5.4 and Stata 15. Statistical heterogeneity was assessed using I 2; a fixed-effect model was used when I 2 < 50%, and a random-effects model when I 2 ≥ 50%. Subgroup analyses, sensitivity analyses, and publication-bias assessments were conducted. Results Twenty-one randomized controlled trials were included. Exercise interventions were associated with significantly lower leptin levels than control conditions based on 18 comparisons (SMD = −0.32, 95% CI [−0.47 to −0.18], P < 0.0001), with low between-study heterogeneity ( I 2 = 22%). Exercise interventions were also associated with significantly higher ghrelin levels based on nine comparisons (SMD = 0.45, 95% CI [0.11–0.79], P = 0.01), although heterogeneity was substantial ( I 2 = 74%). Subgroup analyses suggested that exercise-related characteristics may partly contribute to variability in leptin and ghrelin responses, but these findings were exploratory. Leave-one-out sensitivity analyses supported the stability of the main estimates. For leptin, Egger’s test suggested possible funnel-plot asymmetry, but trim-and-fill analysis did not impute any missing comparison and the pooled estimate remained unchanged. Conclusion Exercise interventions were associated with reduced leptin levels and increased ghrelin levels in middle-aged and older adults with overweight or obesity. The leptin finding appeared relatively consistent, whereas the ghrelin finding should be interpreted cautiously because of fewer comparisons and substantial heterogeneity. Subgroup findings remain exploratory and should not be used to define an optimal exercise prescription. Further randomized controlled trials with more standardized exercise protocols, clearer dietary control, and consistent hormone measurement are needed to clarify the clinical relevance of these changes.