Background and Objective: Mitochondrial DNA copy number (mtDNA-CN) is a dynamic biomarker reflecting mitochondrial content and function, which is sensitive to metabolic stress. However, it remains unclear whether subtle variations in body mass index (BMI) within a healthy population are associated with alterations in mtDNA-CN. This study aimed to determine the association between mtDNA-CN and BMI in healthy adult men.
Materials and Methods: This cross-sectional study involved 32 healthy adult men categorized by BMI into normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²) groups. Genomic DNA was extracted from peripheral blood leukocytes. Relative mtDNA-CN was quantified using real-time PCR by measuring a short mitochondrial DNA fragment relative to the nuclear-encoded β-globin gene.
Results: A significant negative exponential correlation was found between BMI and mtDNA-CN (R = 0.486, p = 0.006). Group comparisons revealed a significant difference in mtDNA-CN across BMI categories (P < 0.05). Specifically, mtDNA-CN was significantly lower in both the overweight and obese groups compared to the normal-weight group, but no significant difference was observed between the overweight and obese groups (P > 0.05).
Conclusion: This study demonstrates a significant inverse association between BMI and mtDNA-CN in healthy adult men, indicating that increased adiposity is linked to reduced mitochondrial abundance even in the absence of clinical disease. The most pronounced decline occurs during the transition from a normal to an overweight BMI, suggesting a potential threshold effect. These findings position mtDNA-CN as a sensitive, early-warning biomarker for subclinical metabolic strain.