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Role of circulating S100A4 protein in obesity: a case-control study in prepuberal children
- Andrea Méndez-Gutierrez, Augusto Anguita-Ruiz, Azahara I. Ruperez, Rosaura Leis, Gloria Bueno, Mercedes Gil-Campos, ANGEL. GIL, Concepción M. Aguilera
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E381
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- Article
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Introduction:
Childhood obesity is considered one of the most serious public health problems of the 21st century. Obesity-associated inflammation could be one of the mechanisms that triggers insulin resistance that could drive systemic alterations such as metabolic disorder. Recently, circulating levels of S100A4 has been associated with insulin resistance and subcutaneuous white adipose tissue inflammation independently of body mass index (BMI) in a cohort of obese adults. Nonetheless, the link between S100A4 and insulin resistance in children is still not known yet. Thus, the aim of the study was to determine if S100A4 plasma levels were associated with insulin resistance status in a cohort of prepuberal children.
Material and methods:In this case-control multicentre study, 250 prepuberal children took part and were stratified in six groups according to sex, obesity stage and insulin resistance status. Blood samples were withdrawn in resting conditions after an overnight fasting. Anthropometric measurements and a routine biochemical analyses were performed. Homeostasis model assessment for insulin resistance index (HOMA-IR) was calculated using fasting plasma glucose and insulin values. S100A4 plasma levels were determined by ELISA CSBEL02032HU (Cusabio Biotech, Wuhan, China).
Results:A lineal multiple regresión (α = 0.05) identified a significative association between S100A4 plasma levels and HOMA-IR in the cohort; each HOMA-IR increasing unit correlated with an increase of 0.008mg/dL in S100A4 plasma levels. (SE = 0.003 and p = 0.02). Moreover, we also observed a positive significative association between S100A4 plasma levels and glucose blood levels (p = 0.005) and BMI (p = 0.008). Inter-group comparations analyses revealed significative differences between normal-weight and insulino-resistant obese boys (p = 0.024). The same result was obtained between normal-weight and insulino-resistant obese girls (p = 0.04), finding a higher S100A4 concentration in insulino- resistant children. As expected, plasma S100A4 levels were also higher in obese children versus normal-weight children (p = 0.02).
Discussion:These data could be clinical relevant due to the possible potential of S100A4 protein as a new circulating biomarker of resistance insulin in a cohort of prepuberal children. These results are supported by other studies in obese adults and adolescents. In conclusion, these results suggest that S100A4 is associated with obesity and insulin resistance in prepuberal children. However, more studies are needed to study the implication and mechanism of this protein in the development of insulin resistance.
Towards a novel marker of insulin resistance in obesity: S100A4 in girls along the puberty. The longitudinal study “PUBMEP”
- Augusto Anguita-Ruiz, Andrea Méndez-Gutierrez, Azahara I. Ruperez, Rosaura Leis, Gloria Bueno, Mercedes Gil-Campos, Angel Gil, Concepción M. Aguilera
-
- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E646
-
- Article
-
- You have access Access
- Export citation
-
Introduction:
Insulin resistance (IR) is the major driver for the development of obesity-associated metabolic and cardiovascular complications. It is well known that IR increase physiologically during puberty; hence, pubertal maturation might favour this metabolic risk in obese children. Recently, a study carried out in adult women with obesity has identified a new adipokine, known as S100A4, strongly associated with IR and inflammation in adipose tissue. On the contrary, little is known about the implication of S100A4 in the development of such metabolic disturbances during the onset and course of pubertal development.
Materials and methods:A longitudinal study was conducted on 53 Spanish girls distributed in six experimental conditions according to their obesity and IR status (before (T0) and after (T1) the onset of puberty). Anthropometric and biochemical parameters were evaluated in all samples and time points. Classification of pubertal stage was made according to the Tanner scale. S100A4 protein levels were quantified by ELISA CSB-EL02032HU in plasma samples (Cusabio Biotech, Wuhan, China). The statistical analysis of the results was carried out with the “nlme” package in R v3.4.4, using a mixed-effects linear model with random intercept and slope.
Results:At a significance level of alpha = 0.05, a linear mixed-effects model reported a significant association (P = 0.03) between the interaction term “time*experimental group” and S100A4 levels. Post-hoc pairwise comparisons between experimental groups revealed a strong association between a worsening/improvement of the IR status and the increase/decrease of S100A4 levels (yielding significant results for 5 of the 15 comparisons (P = 0.008, P = 0.04, P = 0.02, P = 0.04 and P = 0.02)). Furthermore, a multiple linear regression model reported a positive correlation between the increase in S100A4 levels and the increase in HOMA values during the course of puberty (B = 6.03, SE = 2.66 and P = 0.028).
Discussion:The S100A4 protein is strongly associated with the development of IR in girls with childhood obesity and this association is accentuated during pubertal development. Increase in S100A4 levels could be one of the molecular mechanisms by which pubertal maturation favour an increased metabolic risk in children with obesity.