Central adiposity and α-klotho: inflammatory mechanisms underlying aging biomarkers related to body roundness index

Background Obesity is a global health issue which has been widely accepted as an aging related pathogenesis. alpha-Klotho is a protein involved in aging process, mineral metabolism, insulin sensitivity, and the pathogenesis of various age-related diseases. Adiposity correlates with lower soluble alpha-Klotho, but the role of fat distribution and inflammation remains unclear. The body roundness index (BRI) refines central adiposity assessment beyond BMI. Herein, We aimed to investigate the relationship of BRI, inflammation and serum level of soluble alpha-Klotho. Methods We conducted a cross-sectional analysis of 9,958 U.S. adults (40-79 years) from the 2007-2016 NHANES. We examined association between BRI and serum alpha-Klotho (S alpha Kl) levels, controlling for demographic, socioeconomic, lifestyle, and clinical factors. We also assessed whether inflammatory markers mediated the BRI-S alpha Kl relationship. Results BRI was inversely associated with S alpha Kl levels (P < 0.05). A significant sex interaction was found (P < 0.001), while BRI was positively correlated with multiple proinflammatory markers, which were all inversely related to S alpha Kl levels. Mediation analyses showed inflammatory markers accounted for 20.5% (WBC), 18.0% (neutrophils), and 12.3% (platelets) of the BRI-S alpha Kl association. Conclusion More severe central adiposity measured by BRI was related to lower S alpha Kl, which may partly be attributed to inflammation. These findings underscore the importance of fat distribution and inflammation in obesity-related aging and may guide interventions to preserve S alpha Kl levels. Longitudinal studies are needed to confirm causality and inform future strategies.