Resistance-interval training combined with Chlorella vulgaris supplementation modulates PCSK9, ghrelin, adropin, and MANF in obese men: a randomized controlled trial

Obesity disrupts lipid metabolism, appetite regulation, vascular function, and cellular homeostasis through interconnected pathophysiological mechanisms, increasing cardiometabolic disease risk. This randomized controlled trial examined whether 12 weeks of resistance-interval training (RIT) and Chlorella vulgaris supplementation (1800 mg/day), alone or combined, produce coordinated improvements in proprotein convertase subtilisin/kexin type 9 (PCSK9), liver-expressed antimicrobial peptide 2 (LEAP-2), ghrelin, adropin, and mesencephalic astrocyte-derived neurotrophic factor in obese men. Forty-four participants (BMI: 32.0 ± 1.5 kg·m⁻ 2 ; age: 23–35 years) completed the trial across four groups ( N = 11 each): control (CON), Chlorella vulgaris supplementation, RIT, and combined (RIT+SUPP). Two-way mixed ANOVA revealed significant Time × Group interactions for all biomarkers ( P < 0.001). The RIT+SUPP group demonstrated the largest responses: PCSK9 decreased by ~ 40% ( P < 0.001, d = − 2.27), LEAP-2 decreased ( P < 0.001, d = − 2.46), ghrelin increased ( P < 0.001, d = 2.48), adropin increased 49% ( P < 0.001, d = 2.37), and MANF decreased by ~ 55% ( P < 0.001, d = − 2.45). Combining RIT with Chlorella vulgaris produces coordinated, favorable adaptations across lipid, appetite-regulatory, vascular, and cellular stress pathways, representing an accessible, non-pharmacological strategy for comprehensive cardiometabolic risk reduction in obesity. Trial registration : Registered at the Iranian Registry of Clinical Trials. Registration ID IRCT 20260417069089N1.