Circulating low- and medium-molecular-weight adiponectin are associated with metabolic phenotypes in adults undergoing cardiometabolic screening

Background and aims Adiponectin circulates as multimers with potentially distinct biological roles, yet most human studies report total adiponectin, which may mask multimer-specific metabolic information . This study aimed to determine whether circulating low- (LMW) and medium-molecular-weight (MMW) adiponectin and their relative pattern are associated with cardiometabolic, behavioral, and chrononutrition characteristics in adults undergoing screening for the RIO Study. Methods and results In this cross-sectional study, 112 adults who completed the screening assessment for the RIO Study underwent anthropometric/body-composition assessment, fasting biochemistry, self-reported physical activity and sitting time, and chrononutrition evaluation. Serum adiponectin multimers were quantified by Western immunoblotting; under the present experimental conditions, only low-molecular-weight (LMW) and medium-molecular-weight (MMW) multimers were consistently detectable. Associations were assessed using Pearson correlations, adjusted multiple linear regression, and principal component analysis (PCA). Exploratory correlations suggested associations of MMW adiponectin and the MMW/LMW ratio with several anthropometric and metabolic variables. However, after multivariable adjustment, most associations with adiposity and lipid variables were attenuated, whereas inverse associations with GGT and ALT persisted. MMW adiponectin remained inversely associated with GGT (β=−0.37, p < 0.001) and ALT (β=−0.32, p = 0.002). Physically active participants had higher MMW adiponectin and MMW/LMW ratios than inactive participants (FDR-adjusted p < 0.05). Exploratory PCA identified five components with eigenvalues >1, together explaining 66.6% of the total variance. LMW and MMW adiponectin contributed to the multivariate structure, including a shared adiponectin-related component. Conclusion In this cardiometabolic screening cohort, MMW adiponectin and the MMW/LMW ratio showed persistent inverse associations with selected liver-enzyme measures, particularly GGT and ALT, after adjustment for potential confounders. These exploratory findings support further investigation of LMW and MMW adiponectin as metabolic biomarkers using longitudinal and interventional designs.