Objective: Spexin (SPX) is a novel peptide implicated in food intake and satiety. SPX levels are reduced in obese patients. Aim: This study aimed to compare serum SPX levels in obese adolescents versus healthy controls and to assess the associations of metabolic syndrome (metS) antecedents with serum SPX levels. Methods: Eighty consecutive obese adolescents aged 10–18 years and 80 healthy peers were enrolled. Anthropometric measurements, pubertal examinations, and clinical blood pressure measurements were performed. Fasting blood samples were drawn for glucose, insulin, lipids, uric acid, alanine aminotransferase (ALT), and SPX. metS was diagnosed using International Diabetes Federation criteria. Associations of serum SPX with clinical and laboratory variables were assessed. Results: Obese adolescents had lower serum SPX levels than healthy peers (50 pg/mL [25–75% IQR: 25–98 pg/mL] and 67.0 pg/mL [25–75% IQR: 32.5–126.0 pg/mL]; respectively, p = 0.035). Twenty (25%) obese adolescents were diagnosed as having metS. Obese adolescents with metS had lower SPX than those without metS (24.5 pg/mL [25–75% IQR: 15.3–49.5 pg/mL] and 69.0 pg/mL [25–75% IQR: 42.0–142.0 pg/mL]; respectively, p < 0.0001). The frequencies of hyperuricemia, IR, and elevated ALT were similar in obese adolescents with metS and those without metS (p > 0.05 for all). Serum uric acid levels were correlated significantly with serum SPX after correcting for BMI and HOMA-IR (r = −0.41, p < 0.05). A serum SPX level at a cutoff level of 49.5 pg/mL predicted the presence of metS in obese adolescents with 75% sensitivity and 71% specificity. Conclusions: Obese adolescents have reduced SPX levels, and this reduction is more pronounced in those with metS. Further research is needed to verify the utility of SPX as a biomarker in the diagnosis of metS in obese adolescents.

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