S100A4 is a metastasis-associated protein also reported as a promising marker for dysfunctional white adipose tissue (WAT) and insulin resistance (IR) in adult and adolescent populations. We report for the first time the association of S100A4 with IR and WAT dysfunction in prepubertal populations as well as how the change in plasma S100A4 levels accompanies longitudinal trajectories of IR in children during pubertal development. The study design consisted of three cross-sectional populations of 249, 11 and 19 prepubertal children respectively and a longitudinal population of 53 girls undergoing sexual maturation. All of them were recruited in three Spanish hospitals in Galicia, Zaragoza and Córdoba. S100A4 plasma levels were strongly associated with several metabolic and anthropometric outcomes, namely IR, in prepubertal non-diabetic obese children. We also found highly significant positive associations during the course of puberty between the increase in S100A4 levels and the increase in HOMA-IR (P = 0.0003, FDR = 0.005) and insulin levels (P = 0.0003, FDR = 0.005). Moreover, we propose epigenetic changes in two methylation sites and an altered S100A4 vWAT expression as plausible molecular mechanisms underlying this disturbance in obesity. Methylation in two-enhancer related CpG sites of the S100A4 region (cg07245635 and cg10447638) was associated with IR biomarkers at the prepubertal stage and with longitudinal changes in these measurements. We further reported an association between visceral WAT (vWAT) S100A4 expression and HOMA-IR, insulin levels and BMI Z-Score, but not with circulating S100A4.

Referencia completa:

Anguita-Ruiz A, Mendez-Gutierrez A, Ruperez AI, Leis R, Bueno G, Gil-Campos M, Tofe I, Gomez-Llorente C, Moreno LA, Gil Á, Aguilera CM. The protein S100A4 as a novel marker of insulin resistance in prepubertal and pubertal children with obesity. Metabolism. 2020 Feb 18;105:154187..

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