Associations Between Circulating Spexin, Obesity, and Insulin Resistance in Korean Children and Adolescents

<b>Background:</b> Spexin is a neuropeptide involved in various physiological functions, including energy metabolism, appetite regulation, and weight loss. This study aimed to identify correlations between circulating spexin levels, obesity, and insulin resistance (IR) in Korean children and adolescents. <b>Methods:</b> We included 128 Korean children and adolescents in the study. Among them, 69 individuals (53.9%) were classified as obese, 43 (33.6%) were considered overweight, and 16 (12.5%) had a normal weight. We recorded participants' anthropometric parameters, fasting biochemical parameters, and homeostasis model assessment for insulin resistance (HOMA-IR), and assessed their correlations with plasma spexin levels. <b>Results:</b> Plasma spexin levels were significantly lower in obese subjects than in controls (mean, 163.1 vs. 198.4 pg/mL; <i>p</i> = 0.01). Subjects with IR had lower spexin levels than those without IR (mean, 145.3 vs. 185.1 pg/mL; <i>p</i> < 0.001). Spexin levels were negatively correlated with the BMI SDS (r = -0.30; <i>p</i> < 0.001), systolic blood pressure (r = -0.33; <i>p</i> < 0.001), fasting insulin (r = -0.41; <i>p</i> < 0.001), HOMA-IR value (r = -0.41; <i>p</i> < 0.001), triglyceride (TG) level (r = -0.38; <i>p</i> < 0.001), and plasma leptin level (r = -0.26; <i>p</i> = 0.004). In multivariate analysis, HOMA-IR and TG levels were independently associated with plasma spexin levels (<i>p</i> < 0.001 for both). Mediation analyses suggest a potential bidirectional relationship between obesity-related reductions in circulating spexin and insulin resistance. <b>Conclusions:</b> Decreased circulating spexin levels were associated with obesity and IR among Korean children and adolescents. Our findings suggest a link between circulating spexin, obesity, and IR in this population.