The Spexin gene is considered the most dysregulated in obese human fat. Limited data suggest that the novel peptide spexin may potentially impact food intake, weight regulation and body adiposity. The aim of this case-control study was to compare fasting serum spexin concentrations between normal weight (NW) and overweight/obese (OB/OW) adolescent females and explore the relationship between circulating spexin and anthropometric, bone and fat mass, metabolic and hormonal parameters. Eighty post-menarcheal females (mean age ± SD 16.23 ± 2.26 years); 55 NW (mean BMI ± SD 19.72 ± 2.52 kg/m²) and 25 OB/OW (mean BMI ± SD 29.35 ± 3.89 kg/m²) participated in the study. Circulating spexin levels did not differ significantly (p = 0.378) between NW (median (interquartile range), 0.26 (0.17) ng/mL) and OB/OW (median (interquartile range), 0.28 (0.06) ng/mL) adolescents and did not correlate with BMI (r_s = -0.090, p = 0.438), % body fat (r_s = -0.173, p = 0.409), glucose or insulin resistance indices derived from fasting and oral glucose tolerance states. In the total study sample, spexin concentrations correlated positively with lipoprotein(a) (r_s = 0.402, p = 0.046). In the OB/OW adolescents spexin levels correlated positively with testosterone (r_s = 0.727, p = 0.011) and free androgen index (r_s = 0.755, p = 0.007). In the NW adolescents, spexin concentrations correlated negatively with dehydroepiandrosterone sulphate (r_s = -0.445, p = 0.038). Results may suggest potential involvement of spexin in the regulation of lipoprotein(a) and of the reproductive/adrenal axis in post-menarcheal adolescent females.

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