Whole brain gray matter volume may mediate the relationship between light physical activity and Body Mass Index in middle-aged Japanese adults.

Obesity is a multifactorial condition that cannot be fully explained by traditional energy-balance models. Recent studies highlight the role of brain structure-particularly gray matter volume-as a potential risk factor of obesity. Physical activity (PA) has been shown to enhance gray matter volume, particularly in older adults. While prior studies have linked physical activity (PA) with both brain structure and Body Mass Index (BMI), few have examined whether brain structure may account for the association between PA and obesity. Therefore, this study explored the potential mediating role of brain structure in the association between PA and BMI in a cross-sectional sample of Japanese adults. PA was assessed using the Japanese version of the International Physical Activity Questionnaire - Short Form (IPAQ-SF). PA was assessed across three intensity levels (Intense, Moderate, and Light), in terms of duration (minutes per week) and frequency (number of days per week). Brain structure was measured as total gray matter volume, using the Gray Matter Brain Healthcare Quotient (GM-BHQ). Multiple hierarchical linear regression revealed only light PA had individual associations with increased GM-BHQ (R = 0.803, b = 0.188, p = 0.002) and decreased BMI (R = 0.303, b = -0.165, p = -0.096). GM-BHQ also showed a stronger association with BMI than PA alone (R = 0.367, b = -0.313, p = 0.030). Path analysis revealed a potential mediating role of brain structure in the link between PA and BMI (indirect effect = 0.052, p = 0.030). These findings offer new insights into the neurobiological mechanisms underlying obesity and highlight the potential of brain health as a key factor in weight regulation strategies.