Molecular Diagnostics Based on a Metabolite Risk Score Constructed Using Bilirubin and Oleic Acid in Korean Individuals with Obesity

<b>Background/Objectives</b>: Obesity is currently diagnosed by anthropometric measures such as body mass index and waist circumference, while molecular-based diagnostic approaches have not yet been established. The present study aims to investigate the clinical meaning of a metabolite risk score (MRS) from the perspective of molecular diagnostics for obesity in Koreans. <b>Methods</b>: A total of 200 plasma samples were collected from 100 healthy individuals and 100 individuals with obesity through the Korea Biobank Network. Both groups were sub-divided into a discovery set and a validation set (<i>n</i> = 50 per group in each set). Metabolite profiling, cytokines, and oxidized (ox)-LDL were analyzed cross-sectionally. The MRS was constructed using statistically significant metabolites chosen based on linear regression analysis. <b>Results</b>: In the discovery set, systolic blood pressure, tumor necrosis factor-α, and interleukin-6 emerged as conventional obesity-related factors. Bilirubin and oleic acid were selected as key metabolites significantly associated with obesity. The MRS equation was constructed using these key metabolites through a weighted approach. In the validation set, the MRS demonstrated acceptable diagnostic accuracy for obesity (AUC = 0.748, <i>p</i> = 0.005). Furthermore, its diagnostic performance was enhanced when combined with the conventional obesity-related factors (AUC = 0.816, <i>p</i> < 0.001). <b>Conclusions</b>: The MRS, calculated using bilirubin and oleic acid, effectively complemented conventional obesity-related factors in the diagnosis of obesity. Although the MRS currently serves as a supportive molecular framework for obesity assessment, future refinement may improve its performance and broaden its applicability to other metabolic diseases.