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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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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 Blood samples were withdrawn in resting conditions after an overnight fasting.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.
Plasma tocopherols and carotenes are decreased in Spanish metabolically unhealthy children and adolescents independently of obesity
- Azahara I. Rupérez, Gloria Bueno, Rosaura Leis, Mercedes Gil-Campos, Ángel Gil, Luis A. Moreno, María D. Mesa, 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, E136
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Introduction
Childhood obesity is associated with multiple cardio-metabolic abnormalities. A sensitive hypothesis underlying these alterations is oxidative stress, shown to be present in obesity, often accompanied by a diminished antioxidant defense. Specifically, plasma vitamin concentrations have been observed to be associated with obesity in adults and children. However, their association with cardio-metabolic alterations in children is less clear.
Materials and Methods985 children (49.2% males, 71.7% prepubertal, 71.9% excess weight) were recruited in a case-control study of obesity in three Spanish hospitals. Pubertal status was assessed and anthropometry (weight, height), systolic and diastolic blood pressure (SBP, DBP) and serum glucose, insulin, triacylglycerols (TAG) and high-density lipoprotein cholesterol (HDL-C) were measured. Plasma concentrations of tocopherols and carotenes were determined with HPLC-MS and referred to TAG. Children were classified as MU if showing one or more of these criteria: SBP or DBP ≥ 90th percentile (age, sex, height), serum TAG > 90th percentile (age, sex), HDL-C < 10th percentile (age, sex), glucose ≥ 100 mg/dL or elevated HOMA-IR (≥ 2.5 prepubertal, ≥ 3.38 pubertal males, ≥ 3.905 pubertal females). Non-fulfillment was indicative of MH status. General linear models adjusted for sex, age, recruitment center and BMI were used to evaluate differences in vitamins between MH and MU children.
ResultsPrepubertal and pubertal children with excess weight showed lower tocopherols (Pre: 0.133 ± 0.061 vs 0.165 ± 0.065, P < 0.001; Pub: 0.120 ± 0.057 vs 0.163 ± 0.066, P < 0.001) and carotenes (Pre: 15.63 ± 13.72 vs 30.31 ± 26.04, P < 0.001; Pub: 12.34 ± 9.86 vs 22.98 ± 19.25, P < 0.001) plasma concentrations than normal-weight children. MU prepubertal and pubertal children showed lower tocopherols (Pre: 0.120 ± 0.056 vs 0.165 ± 0.064, P < 0.001; Pub: 0.111 ± 0.051 vs 0.154 ± 0.066, P < 0.001) and carotenes (Pre: 14.07 ± 12.61 vs 25.97 ± 21.94, P < 0.001; Pub: 10.90 ± 8.54 vs 19.03 ± 14.58, P < 0.001) plasma concentrations than MH children, independently of BMI. Individual MU components analyses showed similar associations between tocopherols and carotenes and insulin resistance, low HDL-C values and hypertriglyceridemia in prepubertal children; and between tocopherols and carotenes and elevated SBP, hyperglycemia and hypertriglyceridemia in pubertal children.
DiscussionOur findings agree with previous studies that showed decreased plasma concentrations of tocopherols and carotenes in children with obesity. However, we observe further implications of low circulating concentrations of non-enzymatic antioxidants in terms of their negative association with cardio-metabolic alterations such as insulin resistance and dyslipidemia in prepubertal and pubertal children, independently of BMI. These results must be considered when designing prevention and treatment strategies of obesity and its complications.
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
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E646
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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.
Socioeconomically disadvantaged groups and metabolic syndrome in European adolescents: The HELENA study
- Isabel Iguacel, Claudia Börnhorst, Nathalie Michels, Christina Breidenassel, Jean Dallongeville, Marcela González-Gross, Frédéric Gottrand, Anthony Kafatos, Eva Karaglani, Mathilde Kersting, Stefaan de Henauw, Christina-Paulina Lambrinou, Lorenza Mistura, Denes Molná, Esther Nova, Marc J. Gunter, Alejandro de la O. Puerta, Azahara I. Rupérez, Kurt Widhalm, Inge Huybrechts, Luis A. Moreno
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E258
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Introduction:
Psychosocial stressors deriving from socioeconomic disadvantages in adolescents can result in higher metabolic syndrome (MetS) risk. We aimed to examine whether socioeconomic disadvantages were associated with MetS independent of lifestyle and whether there was a dose response relationship between the number of cumulated socioeconomic disadvantages and the risk of MetS.
Materials and Methods:The present study included 1,037 European adolescents (aged 12.5–17.5) of the 3,528 total HELENA participants. Sociodemographic variables and lifestyle were assessed through self-reported questionnaires. Disadvantaged groups included adolescents with low educated parents, low family affluence, migrant origin, unemployed parents, and from non-traditional families. MetS score was calculated as the sum of sex- and age-specific z-scores of waist circumference, HOMA-IR index, mean of z-scores of diastolic and systolic blood pressure and mean of z-score of HDL-C multiplied by -1 and z-score of TG. A higher score indicates poor metabolic health. Linear mixed-effects models were used to study the association between social disadvantages and MetS risk score. Models were adjusted for sex, age, pubertal status (Tanner stage) and lifestyle (diet quality, physical activity, alcohol consumption and smoking status).
Results:Adolescents with low educated mothers showed a higher MetS score (0.54 [0.09–0.98]; β [99% confidence interval]) compared to high-educated mothers. Adolescents who accumulated more than three disadvantages (0.69 [0.08–1.31]) or with missing information on disadvantages (0.72 [0.04–1.40]) had a higher MetS risk compared to non-socioeconomically disadvantaged groups. Stronger associations between socioeconomic disadvantages and MetS were found in male in comparison with female adolescents.
Discussion:Out of the studied socioeconomic disadvantages, maternal education is the most important determinant of adolescent's MetS risk independently of sex, age, Tanner stage, smoking status, alcohol consumption, diet quality and physical activity. Social vulnerabilities (migrant background, unemployment status and belonging to a non-traditional family) were not associated with a higher MetS risk in European adolescents. However, we found a dose-response relationship between the number of factors related to social disadvantage and adolescents’ MetS risk with adolescents accumulating three or more socioeconomic disadvantages showing the highest risk. Stronger associations between socioeconomic disadvantages and MetS were found in male compared to female adolescents. Policy makers should focus on low educated families to tackle health disparities.