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    Unveiling the significance of Netrin-1 and Netrin-4 in metabolic syndrome
    (Nature Portfolio, 2026) Kiran, Tugba Raika; Ayyildiz, Gamze; Keskin, Lezan; Erdem, Mehmet
    Metabolic syndrome (MetS) is characterized by insulin resistance, dyslipidemia, hyperglycemia, and chronic low-grade inflammation. This study aimed to evaluate serum levels of Netrin-1 (NTN1) and Netrin-4 (NTN4) in individuals with MetS and to explore their associations with metabolic and inflammatory parameters. Forty patients with MetS (diagnosed according to the NCEP ATP III criteria) and forty age- and sex-matched healthy controls were included. Serum NTN1 and NTN4 concentrations were measured using enzyme-linked immunosorbent assay (ELISA), together with biochemical and hematological analyses. MetS patients exhibited significantly higher NTN1 (146.66 (54.79) pg/mL) and NTN4 (176.76 +/- 41.65 pg/mL) levels than controls (110.343 (27.14) pg/mL and 133.10 +/- 32.17 pg/mL, respectively; p = 0.001). Binary logistic regression identified NTN4 as a significant variable associated with MetS (p = 0.017), whereas NTN1 did not remain significant after adjustment for other factors. Both markers showed positive correlations with body mass index, fasting glucose, HbA1c, triglycerides, and CRP, and negative correlations with HDL cholesterol (p = 0.001). Receiver operating characteristic (ROC) analysis identified optimal cut-off values for discriminating MetS, with NTN1 >= 122.99 pg/mL yielding 82.5% sensitivity and NTN4 >= 186.49 pg/mL showing 97.5% specificity. Elevated NTN1 and NTN4 levels were associated with the metabolic and inflammatory alterations characteristic of MetS. NTN4, and to a lesser extent NTN1, were associated with systemic metabolic imbalance.