Serum proteome signatures associated with liver steatosis in adolescents with obesity

Purpose Childhood obesity, a pressing global health issue, significantly increases the risk of metabolic complications,including metabolic dysfunction associated with steatotic liver disease (MASLD). Accurate non-invasive tests for early detectionand screening of steatosis are crucial. In this study, we explored the serum proteome, identifying proteins as potentialbiomarkers for inclusion in non-invasive steatosis diagnosis tests.Methods Fifty-nine obese adolescents underwent ultrasonography to assess steatosis. Serum samples were collected andanalyzed by targeted proteomics with the Proximity Extension Assay technology. Clinical and biochemical parameters wereevaluated, and correlations among them, the individuated markers, and steatosis were performed. Receiver operating characteristic(ROC) curves were used to determine the steatosis diagnostic performance of the identified candidates, the fattyliver index (FLI), and their combination in a logistic regression model.Results Significant differences were observed between subjects with and without steatosis in various clinical and biochemicalparameters. Gender-related differences in the serum proteome were also noted. Five circulating proteins, including CathepsinO (CTSO), Cadherin 2 (CDH2), and Prolyl endopeptidase (FAP), were identified as biomarkers for steatosis. CDH2, CTSO,Leukocyte Immunoglobulin Like Receptor A5 (LILRA5), BMI, waist circumference, HOMA-IR, and FLI, among others,significantly correlated with the steatosis degree. CDH2, FAP, and LDL combined in a logit model achieved a diagnosticperformance with an AUC of 0.91 (95% CI 0.75–0.97, 100% sensitivity, 84% specificity).Conclusions CDH2 and FAP combined with other clinical parameters, represent useful tools for accurate diagnosis of fattyliver, emphasizing the importance of integrating novel markers into diagnostic algorithms for MASLD. These data cannot be made publicly available as they include sensitive information, but they can be made available upon reasonable request of interested researchers to the corresponding author, who will forward a data transfer agreement request to the relevant Ethical Committee. Requests can be addressed to Dr. Alessandro Sartorio ([email protected]).