Obesity Science & Practice (Feb 2020)

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity

  • Siri D. Taxerås,
  • María Galán,
  • Laura Campderros,
  • Irene Piquer‐Garcia,
  • Silvia Pellitero,
  • Eva Martínez,
  • Rocío Puig,
  • Icíar Lucena,
  • Jordi Tarascó,
  • Pau Moreno,
  • José Balibrea,
  • Joan Bel,
  • Marta Murillo,
  • María Martínez,
  • Marta Ramon‐Krauel,
  • Manel Puig‐Domingo,
  • Francesc Villarroya,
  • Carles Lerin,
  • David Sánchez‐Infantes

DOI
https://doi.org/10.1002/osp4.381
Journal volume & issue
Vol. 6, no. 1
pp. 99 – 106

Abstract

Read online

Summary Objectives S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. Methods Sixty‐five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty‐nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. Results Circulating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal‐weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment‐insulin resistance (HOMA‐IR) in adults (βstd = .42, P = .008) but not in children (βstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. Conclusions Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti‐inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity.

Keywords