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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 Blood samples were withdrawn in resting conditions after an overnight fasting.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.
Waist-to-height ratio, inflammation and CVD risk in obese children
- Josune Olza, Concepcion M Aguilera, Mercedes Gil-Campos, Rosaura Leis, Gloria Bueno, Miguel Valle, Ramon Cañete, Rafael Tojo, Luis A Moreno, Angel Gil
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- Journal:
- Public Health Nutrition / Volume 17 / Issue 10 / October 2014
- Published online by Cambridge University Press:
- 02 January 2014, pp. 2378-2385
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Objective
To evaluate the association between waist-to-height ratio (WHtR) and specific biomarkers of inflammation, CVD risk and endothelial dysfunction in prepubertal obese children.
DesignProspective, multicentre case–control study matched by age and sex.
SettingChildren were recruited between May 2007 and May 2010 from primary-care centres and schools in three cities in Spain (Cordoba, Santiago de Compostela and Zaragoza).
SubjectsFour hundred and forty-six (223 normal weight and 223 obese) Caucasian prepubertal children aged 6–12 years.
ResultsWHtR was higher in the obese than in the normal-weight children. Blood pressure, waist circumference, weight, height, insulin, plasma lipids, leptin, resistin, abnormal neutrophil and monocyte counts, C-reactive protein, IL-6, IL-8, TNF-α, myeloperoxidase, soluble intercellular adhesion molecule-1, selectin and plasminogen activator inhibitor-1 levels were higher in the obese than in the normal-weight group. Adiponectin and HDL-cholesterol were lower and glucose and metalloproteinase-9 showed no differences. Resistin, TNF-α and active plasminogen activator inhibitor-1 were associated with WHtR, a sensitive indicator of central obesity.
ConclusionsOur results lead to the hypothesis that changes in biomarker levels of insulin resistance, inflammation and CVD risk before puberty might induce metabolic consequences of obesity in obese children before reaching adulthood.
Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials
- Oscar D. Rangel-Huerta, Concepcion M. Aguilera, Maria D. Mesa, Angel Gil
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- Journal:
- British Journal of Nutrition / Volume 107 / Issue S2 / June 2012
- Published online by Cambridge University Press:
- 17 May 2012, pp. S159-S170
- Print publication:
- June 2012
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Inflammation is part of the normal host response to infection and injury. Eicosanoids, cytokines, chemokines, adhesion molecules and other inflammatory molecules are frequently produced during this process. Numerous studies in humans have documented the inflammation-limiting properties of omega-3 fatty acids, but only a few have been randomised clinical trials. The aim of this study was to perform a systematic search of randomised clinical trials on omega-3 fatty acids and inflammatory biomarkers in all subjects including healthy and ill persons up to February 2011 using PubMed and LILACS databases, defined by a specific equation using MeSH terms and limited to randomised clinical trials; there was no any a priori decision to include some diseases and not others. The quality of each publication was validated by using the JADAD scale and the CONSORT checklist. Inflammatory biomarkers were considered as primary outcomes. Twenty-six publications of the last 10 years were selected. Studies included healthy subjects and patients with cardiovascular disease and other chronic and acute diseases; all reported the number of subjects, type of study, type and doses of omega-3 fatty acids, main outcomes and major inflammatory biomarkers. Dietary omega-3 fatty acids are associated with plasma biomarker levels, reflecting lower levels of inflammation and endothelial activation in cardiovascular disease and other chronic and acute diseases, including chronic renal disease, sepsis and acute pancreatitis. However, further research is required before definitive recommendations can be made about the routine use of omega-3 fatty acids in critically ill patients or with neurodegenerative or chronic renal disease.