Peripheral blood mononuclear cells-expressed miRNA profiles derived from children with metabolic-associated fatty liver disease and insulin resistance.

BACKGROUND: miRNA have been proposed as potential biomarkers of metabolic diseases. OBJECTIVES: To identify potential miRNA biomarkers of early metabolic-associated fatty liver disease (MAFLD) and/or insulin resistance (IR) in preadolescent children. METHODS: A total of 70 preadolescents, aged 8.5-12 years old participated in the study. Hepatic fat was assessed by magnetic resonance imaging. Fasting blood biochemical parameters were measured and HOMA-IR calculated. Peripheral blood mononuclear cells (PBMC)-derived miRNA profiles associated with MAFLD (≥5.5% hepatic fat) and IR (HOMA-IR ≥2.5) were identified using untargeted high-throughput miRNAs sequencing (RNA-seq). RESULTS: A total of 2123 PBMC-derived miRNAs were identified in children with (21.4%) or without MAFLD. Among them, hsa-miR-143-3p, hsa-miR-142-5p and hsa-miR-660-5p were up-regulated, and p-hsa-miR-247, hsa-let-7a-5p and hsa-miR-6823-3p down-regulated. Importantly, children with MAFLD had consistently higher miR-660-5p expression levels than their peers without it (p < 0.01), regardless of weight status. A total of 2124 PBMC-derived miRNA were identified in children with IR (28.6%) versus children without IR, where thirteen of them were dysregulated (p < 0.05) in children with IR. In addition, children with IR showed higher levels of miR-374a-5p and miR-190a-5p (p < 0.01) and lower levels of miR-4284 and miR-4791 (p < 005), than their peers without IR in both the whole sample and in those with overweight or obesity. CONCLUSIONS: Our study results suggest circulating miR-660-5p as a potential biomarker of the presence of MAFLD in preadolescent children while circulating miR-320a, miR-142-3p, miR-190a-5p, miR-374a-5p and let-7 family miRNAs could serve as potential biomarkers of IR in children.

Evaluation of Sedentary Behavior and Physical Activity Levels Using Different Accelerometry Protocols in Children from the GENOBOX Study.

BACKGROUND: Physical activity (PA) has acquired a significant relevance due to the health benefits associated with its practice. Accelerometers are an effective tool to assess PA; however, the diversity of cut-off points used to define different PA intensities through accelerometry could interfere in the interpretation of the findings among studies. OBJECTIVES: The present study aimed to examine the sedentary behavior (SB) and physical activity (PA) levels in children using six selected accelerometry protocols based on diverse cut-off points. METHODS: Clinical examination, anthropometric measurements, and PA evaluation by accelerometry were assessed in 543 selected children (10 ± 2.4 years old) from the Spanish GENOBOX study. The ActiLife data scoring program was used to determine daily min spent in SB, and light, moderate, vigorous and moderate-vigorous PA using six validated accelerometry protocols differing in their cut-off points. RESULTS: Very different estimations for SB and PA intensity levels were found in children, independently of the non-wear-time algorithm selected, and considering puberty stages, age and body mass index. The time spent in daily SB varied from 471 to 663.7 min, PA ranged from 141 to 301.6 min, and the moderate-vigorous PA was reported between 20.7 and 180.2 min. CONCLUSION: The choice of a particular accelerometry protocol considering these factors is important to evaluate SB or PA intensities to suit the characteristics of the sample researched. It seems necessary to establish future lines of research that include different analytical approaches to measure SB and PA by accelerometry based on standardized and validated methodology.

Omics Approaches in Adipose Tissue and Skeletal Muscle Addressing the Role of Extracellular Matrix in Obesity and Metabolic Dysfunction.

Extracellular matrix (ECM) remodeling plays important roles in both white adipose tissue (WAT) and the skeletal muscle (SM) metabolism. Excessive adipocyte hypertrophy causes fibrosis, inflammation, and metabolic dysfunction in adipose tissue, as well as impaired adipogenesis. Similarly, disturbed ECM remodeling in SM has metabolic consequences such as decreased insulin sensitivity. Most of described ECM molecular alterations have been associated with DNA sequence variation, alterations in gene expression patterns, and epigenetic modifications. Among others, the most important epigenetic mechanism by which cells are able to modulate their gene expression is DNA methylation. Epigenome-Wide Association Studies (EWAS) have become a powerful approach to identify DNA methylation variation associated with biological traits in humans. Likewise, Genome-Wide Association Studies (GWAS) and gene expression microarrays have allowed the study of whole-genome genetics and transcriptomics patterns in obesity and metabolic diseases. The aim of this review is to explore the molecular basis of ECM in WAT and SM remodeling in obesity and the consequences of metabolic complications. For that purpose, we reviewed scientific literature including all omics approaches reporting genetic, epigenetic, and transcriptomic (GWAS, EWAS, and RNA-seq or cDNA arrays) ECM-related alterations in WAT and SM as associated with metabolic dysfunction and obesity.

Relationship between Physical Activity, Oxidative Stress, and Total Plasma Antioxidant Capacity in Spanish Children from the GENOBOX Study.

The World Health Organization has recommended performing at least 60 min a day of moderate-to-vigorous physical activity (MVPA) and reducing sedentarism in children and adolescents to offer significant health benefits and mitigate health risks. Physical fitness and sports practice seem to improve oxidative stress (OS) status during childhood. However, to our knowledge, there are no data regarding the influence of objectively-measured physical activity (PA) and sedentarism on OS status in children and adolescents. The present study aimed to evaluate the influence of moderate and vigorous PA and sedentarism on OS and plasma total antioxidant capacity (TAC) in a selected Spanish population of 216 children and adolescents from the GENOBOX study. PA (light, moderate, and vigorous) and sedentarism (i.e., sedentary time (ST)) were measured by accelerometry. A Physical Activity-Sedentarism Score (PASS) was developed integrating moderate and vigorous PA and ST levels. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and isoprostane F2α (F2-IsoPs), as markers of OS, were determined by ELISA; and TAC was estimated by colorimetry using an antioxidant kit. A higher PASS was associated with lower plasma TAC and urinary 8-OHdG and F2-IsoPs, showing a better redox profile. Reduced OS markers (8-OHdG and F2-IsoPs) in children with higher PASS may diminish the need of maintaining high concentrations of antioxidants in plasma during rest to achieve redox homeostasis.

Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial.

BACKGROUND: Metformin, a first-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention. METHODS: The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group. RESULTS: Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumption. CONCLUSION: Further studies with a large sample size controlled by lifestyle patterns are required in obese children and adolescents to clarify whether metformin might trigger gut microbiota alterations. TRIAL REGISTRATION: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.

Cluster Analysis of Physical Activity Patterns, and Relationship with Sedentary Behavior and Healthy Lifestyles in Prepubertal Children: Genobox Cohort.

Sedentary habits during childhood are associated with adverse health outcomes. The aim of this work was to cluster lifestyle behaviors and metabolic biomarkers to establish different patterns in children. Their physical and sedentary activities were evaluated by accelerometry, and questionnaires that included lifestyle behaviors, such as adherence to a Mediterranean diet, anthropometry and blood biochemical markers. Cluster analysis was performed to establish different groups based on physical activity levels. A total of 489 children were finally selected. Cluster 1 included children with a mostly sedentary state, whereas Cluster 3 included the most active children and Cluster 2 included children that did not fit into either the sedentary or the highly active groups. In Cluster 3, 56% of children were in a sports club, and a lower percentage used electronic devices in their rooms compared to the other groups. Cluster 1 children exhibited higher insulin, HOMA-IR and triacylglycerides with respect to the other groups. No differences were found regarding adherence to a Mediterranean diet. The choice to practice an extracurricular sport could be an influencing factor to increase exercise and ensure an active lifestyle in children. Reducing or limiting screen time mainly in children's rooms could contribute to an active lifestyle.

Circulating miRNAs as Biomarkers of Obesity and Obesity-Associated Comorbidities in Children and Adolescents: A Systematic Review.

Early detection of obesity and its associated comorbidities in children needs priority for the development of effective therapeutic intervention. Circulating miRNAs (microRNAs) have been proposed as biomarkers for obesity and its comorbidities; therefore, we conducted a systematic review to summarize results of studies that have quantified the profile of miRNAs in children and adolescents with obesity and/or associated disorders. Nine studies aiming to examine differences in miRNA expression levels between children with normal weight and obesity or between obese children with or without cardiometabolic diseases were included in this review. We identified four miRNAs overexpressed in obesity (miR-222, miR-142-3, miR-140-5p, and miR-143) and two miRNAs (miR-122 and miR-34a) overexpressed in children with obesity and nonalcoholic fatty liver disease (NAFLD) and/or insulin resistance. In conclusion, circulating miRNAs are promising diagnostic biomarkers of obesity-associated diseases such as NAFLD and type 2 diabetes already in childhood. However, more studies in children, using massive search technology and with larger sample sizes, are required to draw any firm conclusions.

Vitamin D Food Fortification and Nutritional Status in Children: A Systematic Review of Randomized Controlled Trials.

Children are in the risk group for developing hypovitaminosis D. Several strategies are used to reduce this risk. Among these, fortification of foods with vitamin D (25(OH)D) has contributed to the achievement of nutritional needs. This systematic review aims to discuss food fortification as a strategy for maintenance or recovery of nutritional status related to vitamin D in children. The work was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in the International prospective register of systematic reviews (PROSPERO) database (CRD42018052974). Randomized clinical trials with children up to 11 years old, who were offered vitamin D-fortified foods, and who presented 25(OH)D concentrations were used as eligibility criteria. After the selection stages, five studies were included, totaling 792 children of both sexes and aged between two and 11 years. Interventions offered 300-880 IU of vitamin D per day, for a period of 1.6-9 months, using fortified dairy products. In four of the five studies, there was an increase in the serum concentrations of 25(OH)D with the consumption of these foods; additionally, most children reached or maintained sufficiency status. Moreover, the consumption of vitamin D-fortified foods proved to be safe, with no concentrations of 25(OH)D > 250 nmol/L. Based on the above, the fortification of foods with vitamin D can help maintain or recover the nutritional status of this vitamin in children aged 2-11 years. However, it is necessary to perform additional randomized clinical trials in order to establish optimal doses of fortification, according to the peculiarities of each region.

Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases.

The extracellular matrix (ECM) is a network of different proteins and proteoglycans that controls differentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is affected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.

X chromosome genetic data in a Spanish children cohort, dataset description and analysis pipeline.

X chromosome genetic variation has been proposed as a potential source of missing heritability for many complex diseases, including obesity. Currently, there is a lack of public available genetic datasets incorporating X chromosome genotype data. Although several X chromosome-specific statistics have been developed, there is also a lack of readily available implementations for routine analysis. Here, we aimed: (1) to make public and describe a dataset incorporating phenotype and X chromosome genotype data from a cohort of 915 normal-weight, overweight and obese children, and (2) to deeply describe a whole implementation of the special X chromosome analytic process in genetics. Datasets and pipelines like this are crucial to get familiar with the steps in which X chromosome requires special attention and may raise awareness of the importance of this genomic region.

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

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.

A new fructose-free, resistant-starch type IV-enriched enteral formula improves glycaemic control and cardiovascular risk biomarkers when administered for six weeks to elderly diabetic patients.

BACKGROUND: Reducing the dietary glycaemic response has been proposed as a way to reduce the risk of diabetes complications. OBJECTIVE: The aim of the present study was to evaluate the glycaemic control and cardiovascular risk biomarkers in fragile, elderly type 2 diabetes patients after the intake of a new fructose-free diabetes-specific formula enriched with resistant-starch type IV and high in monounsaturated fatty acids. METHODS: Forty-one type 2 diabetes patients aged 78.9 ± 2.8 years were fed exclusively with an enteral diabetes-specific formula for 6 weeks. Data were collected at baseline and after 6 weeks of feeding. Carbohydrate and lipid metabolism and inflammatory and cardiovascular risk biomarkers were measured to evaluated the course of diabetes complications. RESULTS: Blood glycated haemoglobin significantly decreased after the intervention (6.1 ± 0.1 vs. 5.8 ± 0.1 %; p< 0,045), as well as monocyte chemotactic protein-1 and soluble E-selectin (p < 0.05), while soluble vascular cell adhesion molecule and plasminogen activator inhibitor-1 tended to decrease from baseline to 6 weeks (p = 0.084 and p = 0.05, respectively). CONCLUSION: The new product improves glycaemic control and cardiovascular risk without altering lipid metabolism, which is useful for the prevention of diabetic complications. Longer intervention studies are needed in order to validate these results in a larger population.

A new fructose-free, resistant-starch type IV-enriched enteral formula improves glycaemic control and cardiovascular risk biomarkers when administered for six weeks to elderly diabetic patients / Una nueva fórmula enteral enriquecida en almidones resistentes de tipo IV y sin fructosa mejora el control glucémico y los biomarcadores de riesgo cardiovascular cuando se administra durante seis semanas a pacientes diabéticos ancianos

Background: Reducing the dietary glycaemic response has been proposed as a way to reduce the risk of diabetes complications. Objective: The aim of the present study was to evaluate the glycaemic control and cardiovascular risk biomarkers in fragile, elderly type 2 diabetes patients after the intake of a new fructose-free diabetes-specific formula enriched with resistant-starch type IV and high in monounsaturated fatty acids. Methods: Forty-one type 2 diabetes patients aged 78.9 ± 2.8 years were fed exclusively with an enteral diabetes-specific formula for 6 weeks. Data were collected at baseline and after 6 weeks of feeding. Carbohydrate and lipid metabolism and inflammatory and cardiovascular risk biomarkers were measured to evaluated the course of diabetes complications. Results: Blood glycated haemoglobin significantly decreased after the intervention (6.1 ± 0.1 vs. 5.8 ± 0.1 %; p < 0,045), as well as monocyte chemotactic protein-1 and soluble E-selectin (p < 0.05), while soluble vascular cell adhesion molecule and plasminogen activator inhibitor-1 tended to decrease from baseline to 6 weeks (p = 0.084 and p = 0.05, respectively). Conclusion: The new product improves glycaemic control and cardiovascular risk without altering lipid metabolism, which is useful for the prevention of diabetic complications. Longer intervention studies are needed in order to validate these results in a larger population (AU)

Introducción: el control de la respuesta glucémica se ha propuesto como un mecanismo útil para reducir el riesgo de las complicaciones en los diabéticos. Objetivo: evaluar el efecto sobre el control glucémico y el riesgo cardiovascular en ancianos con diabetes de tipo 2 de una nueva fórmula específica para diabéticos, sin fructosa, y que contiene almidones resistentes de tipo IV y un elevado contenido en ácidos grasos monoinsaturados. Métodos: 41 pacientes con diabetes mellitus de tipo 2 y una edad media de 78,9 ± 2,8 años se alimentaron exclusivamente de forma enteral con la fórmula específica para diabéticos durante 6 semanas. Se tomaron muestras al inicio y al final del periodo de intervención y se determinaron biomarcadores del metabolismo de los carbohidratos y lípidos, así como de inflamación y riesgo cardiovascular, con objeto de evaluar el curso de las complicaciones de la diabetes. Resultados: la hemoglobina glicosilada en la sangre disminuyó de forma significativa tras la intervención (6,1 ± 0,1 vs. 5,8 ± 0,1 %; p < 0,045), así como la proteína quimiotáctica de monocitos-1 y la E-selectina soluble (p < 0,05), mientras que la molécula de adhesión vascular y el activador del plasminógeno-1 tendieron a disminuir tras las 6 semanas de intervención (p = 0,084 y p = 0,05, respectivamente). Conclusión: el nuevo producto mejora el control glucémico y el riesgo cardiovascular sin alterar el metabolismo lipídico, lo que resulta útil para la prevención de las complicaciones de los diabéticos. Se necesitan estudios más prolongados para confirmar este efecto en una población más amplia (AU)

Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review.

Over the last several years, the increasing prevalence of obesity has favored an intense study of adipose tissue biology and the precise mechanisms involved in adipocyte differentiation and adipogenesis. Adipocyte commitment and differentiation are complex processes, which can be investigated thanks to the development of diverse in vitro cell models and molecular biology techniques that allow for a better understanding of adipogenesis and adipocyte dysfunction associated with obesity. The aim of the present work was to update the different animal and human cell culture models available for studying the in vitro adipogenic differentiation process related to obesity and its co-morbidities. The main characteristics, new protocols, and applications of the cell models used to study the adipogenesis in the last five years have been extensively revised. Moreover, we depict co-cultures and three-dimensional cultures, given their utility to understand the connections between adipocytes and their surrounding cells in adipose tissue.

An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes.

The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 µM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases.

Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes.

Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX) activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5) were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2) and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes.

Associations among Inflammatory Biomarkers in the Circulating, Plasmatic, Salivary and Intraluminal Anatomical Compartments in Apparently Healthy Preschool Children from the Western Highlands of Guatemala.

BACKGROUND: Undernutrition and inflammation are related in many ways; for instance, non-hygienic environments are associated with both poor growth and immunostimulation in children. OBJECTIVE: To describe any existing interaction among different inflammation biomarkers measured in the distinct anatomical compartments of whole blood, feces, plasma and saliva. METHODS: In this descriptive, cross-sectional study, samples of whole blood, feces, plasma and saliva were collected on the 8th and last week of observation among 87 attendees (42 girls and 45 boys) of 3 daycare centers offering a common 40-day rotating menu in Guatemala's Western Highlands. Analyses included white blood cell count (WBC), fecal calprotectin, and plasmatic and salivary cytokines including IL-1B, IL-6, IL-8, IL-10 and TNF-α. Associations were assessed using Spearman rank-order and goodness-of-fit correlations, as indicated, followed by backwards-elimination multiple regression analyses to determine predictor variables for IL-10 in both anatomical compartments. RESULTS: Of a total of 66 cross-tabulations in the Spearman hemi-matrix, 22 (33%) were significantly associated. All 10 paired associations among the salivary cytokines had a significant r value, whereas 7 of 10 possible associations among plasma cytokines were significant. Associations across anatomical compartments, however, were rarely significant. IL-10 in both biological fluids were higher than corresponding reference values. When a multiple regression model was run in order to determine independent predictors for IL-10 in each anatomical compartment separately, IL-6, IL-8 and TNF-α emerged as predictors in plasma (r2 = 0.514) and IL-1B, IL-8 and TNF-α remained as independent predictors in saliva (r2 = 0.762). Significant cross-interactions were seen with WBC, but not with fecal calprotectin. CONCLUSION: Interactions ranged from robust within the same anatomical compartment to limited to nil across distinct anatomical compartments. The prominence of the anti-inflammatory cytokine, IL-10, in both plasma and saliva is consistent with its counter-regulatory role facing a broad front of elevated pro-inflammatory cytokines in the same compartment.

Urinary osmolality of preschool children with a largely common weekday meal offereing, from the western highlands of Guatemala / Osmolalidad urinaria de niños preescolares con un mismo menú ofrecido durante días hábiles, en el altiplano occidental de Guatemala

Introduction: Urine volume and osmolality are within the most practical methods for measuring human hydration status. Objectives: To describe the distribution and central tendency of urinary osmolality (Uosm) for preschool children, and to assess the reproducibility of Uosm measurements after frozen storage and when determined in two different osmometers. . Methods: We collected three samples of 24-hour urine over three consecutive weeks among children attending three day-care centres in different settings in Quetzaltenango, Guatemala. Volume was determined and samples were stored at different temperatures for different periods of time. Finally, Uosm was measured on two different osmometers in different countries. Data were analyzed using SPSS version 20. Results: Twenty-four hour urine volumes ranged from 65 to 1,670 ml, with a median value of 485 ml; urine osmolality ranged from 158 to 1,088 mOsm/kg, with a median of 475 mOsm/kg (n = 234 urine collections), without differences by sex, centre, or collection order. Seventy-six subjects completed 3 collections; Coefficients of Variation ranged from 1 to 68%. When refrigerated urine samples were compared to split-sample aliquots frozen at -80º, the correlation was r = 0.89 and the difference in medians was 0.2%. Values from frozen samples between a Vogel-Löser 815 and Gonotec-Osmomat 030 had a correlation of r = 0.83, with an 11% difference in the median. Conclusions: Guatemalan children show some of the lowest median Uosm values so far reported. A good reproducibility was found when measuring after different storage times and temperatures, but on the same equipment. However, reproducibility across different osmometer brand, was not within acceptable limits (AU)

Introducción: El volumen y la osmolalidad urinarios son dos de los métodos más prácticos para medir hidratación en humanos. Objetivos: Describir la distribución y tendencia de osmolalidad urinaria (Uosm) en preescolares y determinar los efectos del almacenamiento en congelación y la medición en diferentes osmómetros sobre la reproducibilidad de resultados. Métodos: Se recolectaron tres muestras de orina de 24- horas durante tres semanas, en niños que asistían a tres guarderías de diferentes lugares en Quetzaltenango, Guatemala; se determinó volumen y las muestras fueron conservadas durante diferentes tiempos y temperaturas. Finalmente, la Uosm fue medida en dos diferentes osmómetros y países. Los datos se analizaron usando SPSS versión 20. Resultados: El volumen de orina varió entre 65 y 1.670 ml, con una mediana de 485 mlL; la Uosm entre 158 y 1.088 mOsm/kg con 475 mOsm/kg de mediana, (234 muestras de orina), sin diferencias por sexo, centro ni semana de recolección. 76 sujetos completaron las 3 recolecciones y los CV oscilaron entre 1 y 68%. Al analizar las alícuotas refrigeradas y compararlas con las congeladas (-80ºC), la correlación fue r = 0,89 y la diferencia de medianas fue de 0,2%. Las mediciones de las muestras congeladas entre el Vogel, Löser, y el Gonotec, Osmomat, tuvieron una correlación de r = 0,83 con un 11% de diferencia de medianas. Conclusión: Guatemala tiene uno de los valores más bajos de Uosm observados hasta el momento. Se encontró una buena reproducibilidad en las mediciones en diferentes tiempos y temperaturas, pero en el mismo equipo. La reproducibilidad no fue aceptable entre diferentes marcas de osmómetros (AU)

Changes in plasma adipokines in prepubertal children with a history of extrauterine growth restriction.

OBJECTIVE: Because nutritional support in perinatal life has been associated with metabolic programming, children with a history of extrauterine growth restriction (EUGR) might display alterations in the adipocyte and in the secretion of adipokines. The aim of this study was to assess adiponectin, resistin, and leptin concentrations in prepubertal children with a history of EUGR, and to determine the potential correlation between these adipokines and metabolic parameters. METHODS: This case-control study sample included 38 prepubertal children with a history of EUGR and a control group of 123 healthy children of similar age and sex. Anthropometric measures and blood pressure were assessed. Biochemical markers and blood adipokine concentrations (adiponectin, resistin, and leptin) were evaluated. RESULTS: Adiponectin concentration was significantly lower in the EUGR group compared with controls (EUGR: 11.49 ± 6.07 versus control: 25.72 ± 10.13 µg/mL), and resistin concentration was higher (EUGR: 20332.95 ± 6401.25 versus control: 8056.31 ± 3823.63 pg/mL), even after adjustment for gestational age, weight, and size at birth. Systolic blood pressure was associated with adipokines concentrations in the EUGR group (P < 0.001). In EUGR children adiponectin was associated with high-density lipoprotein cholesterol (P = 0.042), whereas resistin was associated with carbohydrate metabolism parameters (P < 0.001). CONCLUSIONS: Early postnatal malnutrition in EUGR children could program adipose tissue. Plasma adipokines can be measured in childhood to identify precocious changes that may be associated with a higher risk for metabolic syndrome or cardiovascular disease later in life.

Ghrelin: a hormone regulating food intake and energy homeostasis.

Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.