Identification of modifiable plasma protein markers of cardiometabolic risk in children and adolescents with obesity

Pediatric obesity is associated with multi-organ inflammation and an increased risk of cardiometabolic disease. To identify novel biomarkers of early-onset obesity-related cardiometabolic risk, we performed targeted proteomics, analyzing 149 proteins related to inflammation and cardiovascular disease in a cross-sectional sample of 2,377 children and adolescents with overweight/obesity and 1,647 with normal weight. In addition, we analyzed 64 circulating inflammation-related proteins in 184 children and adolescents, who participated in a 1-year family-based obesity management program. We identified a three plasma protein panel (CDCP1, FGF21 and HAOX1) that improved prediction of hepatic steatosis, compared with the predictive value of liver enzymes alone. In the prospective trial, we found that the non-pharmacological intervention induced a decline in circulating inflammatory cytokine levels, some of which were linked to improvements in cardiometabolic phenotypes. Our results may suggest that circulating proteomic signatures may mediate the associations between pediatric obesity and cardiometabolic risk.