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<p>Pediatric obesity is linked to multi-organ inflammation and an increased risk of cardiometabolic and steatotic liver disease. To identify circulating biomarkers of cardiometabolic risk, we performed proximity extension assay proteomics, to quantify 149 inflammation- and cardiovascular-related proteins in a cross-sectional study of 4024 children and adolescents (2377 with obesity and 1647 with normal weight). We identified protein signatures linked to obesity, dyslipidemia, insulin resistance, hyperglycemia, hypertension, and related cardiometabolic phenotypes. Using machine learning, a three-protein panel (CDCP1, FGF21, HAOX1) combined with liver enzymes improved prediction of steatotic liver disease versus liver enzymes alone (receiver operating characteristic–area under the curve (ROC–AUC) = 0.83 vs. 0.77; DeLong’s test, P &lt; 0.05). During a 1-year non-pharmacological obesity intervention (n = 184), reductions in adiposity were associated with decreased inflammatory cytokines (including CDCP1, FGF21), which correlated with improvements in cardiometabolic risk profiles. Here we show that circulating proteomic signatures may mediate obesity-related cardiometabolic risk in youth.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Sara Elizabeth Stinson,
  • Yun Huang,
  • Roman Thielemann,
  • Evelina Stankevic,
  • Morten Asp Vonsild Lund,
  • Louise Aas Holm,
  • Cilius Esmann Fonvig,
  • Helene Bæk Juel,
  • Dmitrii Borisevich,
  • Maja Thiele,
  • Aleksander Krag,
  • Lars Ängquist,
  • Thorkild I. A. Sørensen,
  • Oluf Pedersen,
  • Michael Christiansen,
  • Jens-Christian Holm,
  • Torben Hansen

摘要

Pediatric obesity is linked to multi-organ inflammation and an increased risk of cardiometabolic and steatotic liver disease. To identify circulating biomarkers of cardiometabolic risk, we performed proximity extension assay proteomics, to quantify 149 inflammation- and cardiovascular-related proteins in a cross-sectional study of 4024 children and adolescents (2377 with obesity and 1647 with normal weight). We identified protein signatures linked to obesity, dyslipidemia, insulin resistance, hyperglycemia, hypertension, and related cardiometabolic phenotypes. Using machine learning, a three-protein panel (CDCP1, FGF21, HAOX1) combined with liver enzymes improved prediction of steatotic liver disease versus liver enzymes alone (receiver operating characteristic–area under the curve (ROC–AUC) = 0.83 vs. 0.77; DeLong’s test, P < 0.05). During a 1-year non-pharmacological obesity intervention (n = 184), reductions in adiposity were associated with decreased inflammatory cytokines (including CDCP1, FGF21), which correlated with improvements in cardiometabolic risk profiles. Here we show that circulating proteomic signatures may mediate obesity-related cardiometabolic risk in youth.