Susceptibilidad genética de obesidad y síndrome metabólico en la infancia

Obesity is one of the major public health problems worldwide. It is a chronic, complex, and multifactorialorigin disease characterised by body fat excess mainly due to an imbalance between dietary intake and energy expenditure. One of the major complications of obesity is metabolic syndrome, which comprises anthropometrical, clinical, and metabolic dysfunctions that predispose the affected individual to the development of type 2 diabetes mellitus and cardiovascular diseases. It is hypothesised that the variability in the susceptibility to obesity-mediated metabolic complications involves both environmental and genetic factors. Whereas advances in the knowledge of the variations in the human genome have led to the identification of susceptibility genes that con - tribute to obesity and related disorders, relatively few studies have specifically focused on the interactions bet - ween obesity and genetic polymorphisms and the development of metabolic complications. Despite these limited efforts, an increasing amount of evidence suggests that the effects of some gene variants on metabolic traits are modified by or present only in the setting of obesity. Fur - thermore, some of these loci may have larger effects on metabolic phenotypes in the presence of certain dietary or lifestyle factors. In the present manuscript, we revie - wed the genes and their variants that have been evidenced to play a role in obesity-associated metabolic complications through genetic association studies, including candidate gene and genome-wide association approaches in adults and children.La obesidad es uno de los principales problemas de salud pública a nivel mundial. Es una enfermedad crónica, compleja y de origen multifactorial que se caracteriza por el exceso de grasa corporal y se desarrolla, fundamentalmente, debido a un desequilibrio entre la ingesta dietética y el gasto energético. Una de las principales complicaciones de la obesidad es el síndrome metabólico, el cual comprende alteraciones antropométricas, clínicas y metabólicas que predisponen el desarrollo de diabetes mellitus tipo 2 y enfermedades cardiovasculares.Existe la hipótesis de que tanto factores ambientales como genéticos participan en la variabilidad a la susceptibilidad de las complicaciones metabólicas mediadas por la obesidad. Mientras que los avances en el conocimiento de las variaciones en el genoma humano, han llevado a la identificación de genes que contribuyen a la susceptibilidad de la obesidad y las enfermedades asociadas, son relativamente pocos los estudios que se han centrado específicamente en la interacción entre la obesidad y polimorfismos genéticos relacionados con el desarrollo de complicaciones metabólicas o directamente con el síndrome metabólico. Además, algunos de estos loci pueden tener mayor efecto en los fenotipos metabólicos cuando está modificado por la dieta u otrosfactores ambientales. En este manuscrito se revisan los genes ylas variantes con mayor evidencia de asociación con las complicaciones metabólicasrelacionadas con la obesidad descritas en estudios de asociación genética, incluyendo estudios de genes candidatos y estudios amplios del genoma humano en adultos y niños.This work was supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnoló - gi ca (I + D + I) of the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (PI020826, PI051968), Con - sejería de Innovación y Ciencia of the Junta de Andalucía (P06-CTS 2203), and Ministerio de Universidades y Tecnología of the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, RETIC (Red SAMID RD08/ 0072/0028)

Reported Dietary Intake, Disparity between the Reported Consumption and the Level Needed for Adequacy and Food Sources of Calcium, Phosphorus, Magnesium and Vitamin D in the Spanish Population: Findings from the ANIBES Study

Calcium, phosphorus, magnesium and vitamin D have important biological roles in the body, especially in bone metabolism. We aimed to study the reported intake, the disparity between the reported consumption and the level needed for adequacy and food sources of these four nutrients in the Spanish population. We assessed the reported intake for both, general population and plausible reporters. Results were extracted from the ANIBES survey, n = 2009. Three-day dietary reported intake data were obtained and misreporting was assessed according to the European Food Safety Authority (EFSA). Mean ± SEM (range) total reported consumption of calcium, phosphorus, magnesium, and vitamin D for the whole population were 698 ± 7 mg/day (71–2551 mg/day), 1176 ± 8 mg/day, (331–4429 mg/day), 222 ± 2 mg/day (73–782 mg/day), and 4.4 ± 0.1 µg/day (0.0–74.2 µg/day), respectively. In the whole group, 76% and 66%; 79% and 72%; and 94% and 93% of the population had reported intakes below 80% of the national and European recommended daily intakes for calcium, magnesium and vitamin D, respectively; these percentages were over 40% when the plausible reporters were analysed separately. The main food sources were milk and dairy products for calcium and phosphorus, cereals and grains for magnesium and fish for vitamin D. In conclusion, there is an important percentage of the Spanish ANIBES population not meeting the recommended intakes for calcium, magnesium and vitamin D.The ANIBES study was financially supported by a grant from Coca-Cola Iberia through an agreement with the Spanish Nutrition Foundation (FEN)

Biological evaluation of a protein mixture intended for enteral nutrition

La nutrición enteral (NE) es el mejor recurso para complementar la alimentación de los pacientes, siempre que el tracto gastrointestinal este funcional. Cuando se indica NE total, ésta representa la fuente exclusiva de alimento, por lo que es importante asegurar un alto valor biológico de la proteína incluida. Objetivo: Valorar la calidad biológica de una mezcla proteica constituida por 50% de caseinato potásico, 25% de proteínas de suero lácteo y 25% de proteína de guisante para ser utilizada en productos de nutrición enteral. Material y métodos: 40 ratas Wistar (20 hembras y 20 machos), con peso medio de 51 g, divididas en cuatro grupos. Dos de ellos fueron alimentados con dietas específicas para ratas: uno con caseína (Control) y otro con la proteína experimental (Experimental); los otros fueron alimentados con productos de NE diseñados para humanos y adaptados a los requerimientos de las ratas (Normoproteico e Hiperproteico), durante 10 días. Se determinó el índice de eficacia proteica (PER), el coeficiente de digestibilidad aparente (CDA), la relación nitrógeno retenido/ absorbido (R/A) y la relación nitrógeno retenido/ingerido (R/I). Resultados: El grupo experimental y el grupo control presentaron valores similares en todos los índices analizados. Asimismo, estos índices fueron similares entre los grupos normo e hiperproteicos, pero menores respecto a los grupos anteriores, exceptuando al PER, el cual fue a su vez similar entre el grupo normoproteico y el control. Conclusión: La calidad de la mezcla proteica utilizada es alta y adecuada para ser incluida en el desarrollo de nuevos productos para nutrición enteral.Enteral nutrition is the best way to feed or supplement the diet when gastrointestinal tract functions of patients are partially or totally preserved. Whenever total enteral nutrition is needed, it represents the only source of nutrients for patients. Thus, it is mandatory to ensure that high biological value proteins are included in enteral formulae. Objective: To assess the biological quality of a protein blend constituted by 50% potassium caseinate, 25% whey protein and 25% pea protein intended to be used in enteral nutrition products. Materials and methods: Forty Wistar rats (20 male and 20 female), with initial body weight of 51 g, where divided into four groups and feed for 10 days with: casein (Control), experimental protein blend (Experimental), liophylized normo- and hyperproteic enteral nutrition formulae adapted to the animal nutritional requirements (Normoproteic and Hyperproteic). Protein efficiency ratio (PER), apparent digestibility coefficient (ADC), relationship between retained and absorbed nitrogen (R/A) and relationship between retained and consumed nitrogen (R/I) where calculated. Results: Experimental and control groups had similar values for all analysed indices (PER, ADC, R/A and R/I). These indices where also similar between normo and hyperproteic groups, but lower than experimental and control groups, except in PER, where normoproteic group was either similar to control and hiperproteic group. Conclusion: The quality of the protein blend used in this study is high. It is a good protein source to be used in the development of new enteral nutritional products

Dietary sources and intakes of folates and vitamin B12 in the Spanish population: Findings from the ANIBES study

Background: Folates and vitamin B12 are key nutrients in one-carbon metabolism and related diseases. Updated and plausible information on population intakes and their major dietary sources is scarce and urgently needed in Spain in order to increase the knowledge that can lead as previous step to prevention by fortification and supplementation policies. Aims: The present study aims to evaluate main dietary folate and vitamin B12 sources and intakes in the Spanish population. Materials and methods: Results were derived from the ANIBES cross-sectional study using a nationally representative sample of the Spanish population (9–75 years, n = 2,009). Results: Food groups with the highest mean proportional contribution to total folate intakes in both males and females were vegetables (21.7–24.9%) and cereals (10.7–11.2%), while meat and meat products (26.4%) and milk and dairy products (27.3%) were for B12. Total median folate and B12 intakes amongst women were 156.3 μg/d and 4.0 μg/d while for men were 163.6 μg/d and 4.5 μg/d, respectively. In all age groups, vitamin intakes were significantly higher in plausible than in non-plausible energy reporters. Conclusion: A limited number of participants had adequate folate intakes, whereas vitamin B12 intakes were adequate for practically the entire population. There is a clear need for improving folates intake in the Spanish population.The study was financially supported by a grant from Coca-Cola Iberia through an agreement with the Spanish Nutrition Foundation (Fundación Española de la Nutrición (FEN))

Dietary Intake and Food Sources of Niacin, Riboflavin, Thiamin and Vitamin B6 in a Representative Sample of the Spanish Population. The ANIBES Study

Thiamin, riboflavin, niacin, and vitamin B6 are essential micronutrients that are mainly involved in energy metabolism; they may prevent the occurrence of developmental abnormalities and chronic degenerative and neoplastic diseases. The aim was to analyze dietary intake and food sources of those four nutrients in subjects (n = 2009) aged 9–75 years old from the Spanish ANIBES (Anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles in Spain) study. Dietary data were collected by means of a validated, photo-based three-day dietary food record. Underreporting was analysed according to the European Food and Safety Authority (EFSA, Parma, Italy) protocol. Mean (max–min) reported intake for the whole population of thiamin was 1.17 0.02 mg/day, (0.30–3.44 mg/day), riboflavin 1.44 0.02 mg/day, (0.37–3.54 mg/day), niacin 29.1 0.2 mg/day (6.7–109 mg/day), and vitamin B6 1.54 0.01 mg/day (0.28–9.30 mg/day). The main sources of intake for thiamin, niacin, and vitamin B6 were meat and meat products, and for riboflavin were milk and dairy products. An elevated percentage of the Spanish ANIBES population meets the EFSA recommended intakes for thiamin (71.2%), riboflavin (72.0%), niacin (99.0%), and vitamin B6 (77.2%).The ANIBES study was financially supported by a grant from Coca-Cola Iberia through an agreement with the Spanish Nutrition Foundation (FEN)

Análisis de polimorfismos de genes asociados al síndrome metabólico en niños obesos

Tesis Univ. Granada. Departamento de Bioquímica y Biología Molecular II. Leída el 17 de mayo de 201

Prematurity With Extrauterine Growth Restriction Increases the Risk of Higher Levels of Glucose, Low-Grade of Inflammation and Hypertension in Prepubertal Children

Introduction: An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction. The aim of this study was to assess whether children with a history of prematurity and EUGR, but also with an adequate growth, showed alterations in the metabolic and inflammatory status. Methods: This was a case–control study. A total of 88 prepubertal children with prematurity antecedents were selected: 38 with EUGR and 50 with an adequate growth pattern (PREM group). They were compared with 123 healthy children born at term. Anthropometry, metabolic parameters, blood pressure (BP), C-reactive protein, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, tumour necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor type-1 were analysed at the prepubertal age. Results: EUGR children exhibited higher BP levels and a higher prevalence of hypertension (46%) compared with both PREM (10%) and control (2.5%) groups. Moreover, there was a positive relationship between BP levels and values for glucose, insulin and HOMA-IR only in children with a EUGR history. The EUGR group showed higher concentrations of most of the cytokines analysed, markedly higher TNF-α, HGF and MCP-1 levels compared with the other two groups. Conclusion: EUGR status leads to cardiometabolic changes and a low-grade inflammatory status in children with a history of prematurity, and that could be related with cardiovascular risk later in life.This study was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (Iþ DþI), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria Project No. PI13/01245 from the Spanish Ministry of Health and Consumer Affairs, and was co-financed by the Consejeria de Innovacion y Ciencia, Junta de Andalucía, PI-0480-2012, Spain

Effects of X-chromosome Tenomodulin Genetic Variants on Obesity in a Children’s Cohort and Implications of the Gene in Adipocyte Metabolism

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This paper will be part of Augusto Anguita-Ruiz’s doctorate, which is being performed under the “Nutrition and Food Sciences Program” at the University of Granada.Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-40482-0.Tenomodulin (TNMD) is a type II transmembrane glycoprotein that has been recently linked to obesity, and it is highly expressed in obese adipose tissue. Several sex-dependent associations have been observed between single-nucleotide polymorphisms (SNPs) of the TNMD gene, which is located in the X-chromosome, and obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome in adults. On the other hand, results are lacking for children. We aimed (i) to study the association between TNMD genetic variants and metabolic complications related to childhood obesity and (ii) to investigate the function of TNMD in human adipocytes. We conducted a case-control, multicenter study in 915 Spanish children and demonstrated significant positive associations between TNMD genetic variants and BMI z-score, waist circumference, fasting glucose, and insulin resistance in boys, highlighting the SNP rs4828038. Additionally, we showed a BMI-adjusted inverse association with waist circumference in girls. Second, in vitro experiments revealed that TNMD is involved in adipogenesis, along with glucose and lipid metabolism in differentiated adipocytes, and these effects may be mediated through AMPK activation. Hence, these results suggest that TNMD genetic variants could be potentially useful as early life risk indicators for obesity and T2DM. In addition, we support the fact that TNMD exhibits significant metabolic functions in adipocytes.This work was supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (Projects numbers PI020826, PI051968, PI1102042, PI1600871), RETIC (Red SAMID RD12/0026/0015), Fondo Europeo De Desarrollo Regional (FEDER) and the Junta de Andalucía (project number CTS-6770); Secretaría General de Universidades, Investigación y Tecnología. Consejería de Economía, Innovación y Ciencia)

Prematurity With Extrauterine Growth Restriction Increases the Risk of Higher Levels of Glucose, Low-Grade of Inflammation and Hypertension in Prepubertal Children.

Introduction: An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction. The aim of this study was to assess whether children with a history of prematurity and EUGR, but also with an adequate growth, showed alterations in the metabolic and inflammatory status. Methods: This was a case-control study. A total of 88 prepubertal children with prematurity antecedents were selected: 38 with EUGR and 50 with an adequate growth pattern (PREM group). They were compared with 123 healthy children born at term. Anthropometry, metabolic parameters, blood pressure (BP), C-reactive protein, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, tumour necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor type-1 were analysed at the prepubertal age. Results: EUGR children exhibited higher BP levels and a higher prevalence of hypertension (46%) compared with both PREM (10%) and control (2.5%) groups. Moreover, there was a positive relationship between BP levels and values for glucose, insulin and HOMA-IR only in children with a EUGR history. The EUGR group showed higher concentrations of most of the cytokines analysed, markedly higher TNF-α, HGF and MCP-1 levels compared with the other two groups. Conclusion: EUGR status leads to cardiometabolic changes and a low-grade inflammatory status in children with a history of prematurity, and that could be related with cardiovascular risk later in life