Novel brown adipose tissue candidate genes predicted by the human gene connectome

We would like to thank M. Thomas and R. de Casas for their helpful comments, and C. Osuna, F. Perfectti (CGL2013-47558-P), and the Scientific Supercomputing Center of the Universidad de Granada for sharing computational resources. We are also grateful to Ms. Carmen Sainz-Quinn for assistance with the English language. The study was supported by a Marie S. Curie Global Fellowship within the European Union research and innovation framework programme (2014-2020; ClimAHealth: 101030971). It was also supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393), Fondos Estructurales de la Union Europea (FEDER), by the Fundacion Iberoamericana de Nutricion (FINUT), by the Redes tematicas de investigacion cooperativa RETIC (Red SAMID RD16/0022), by AstraZeneca HealthCare Foundation, by the University of Granada Plan Propio de Investigacion (Excellence actions: Unit of Excellence on Exercise and Health [UCEES]), and by the Junta de Andalucia, Consejeria de Economia, Conocimiento, Empresas y Universidad (ref. P18-624 RT-4455).Brown adipose tissue (BAT) is a promising therapeutic target against obesity. Therefore, research on the genetic architecture of BAT could be key for the development of successful therapies against this complex phenotype. Hypothesis-driven candidate gene association studies are useful for studying genetic determinants of complex traits, but they are dependent upon the previous knowledge to select candidate genes. Here, we predicted 107 novel-BAT candidate genes in silico using the uncoupling protein one (UCP1) as the hallmark of BAT activity. We first identified the top 1% of human genes predicted by the human gene connectome to be biologically closest to the UCP1, estimating 167 additional pathway genes (BAT connectome). We validated this prediction by showing that 60 genes already associated with BAT were included in the connectome and they were biologically closer to each other than expected by chance (p < 2.2 × 10− 16). The rest of genes (107) are potential candidates for BAT, being also closer to known BAT genes and more expressed in BAT biopsies than expected by chance (p < 2.2 × 10− 16; p = 4.39 × 10– 02). The resulting new list of predicted human BAT genes should be useful for the discovery of novel BAT genes and metabolic pathways.Marie S. Curie Global Fellowship within the European Union research and innovation framework programme ClimAHealth: 101030971Spanish Ministry of Economy and Competitiveness, Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393Fondos Estructurales de la Union Europea (FEDER)Fundacion Iberoamericana de Nutricion (FINUT)Redes tematicas de investigacion cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de InvestigacionJunta de Andalucia P18-624 RT-4455 CGL2013-47558-

Association between PTPN1 polymorphisms and obesity-related phenotypes in European adolescents: influence of physical activity

Background To study the associations of Protein Tyrosine Phosphatase-N1 (PTPN1) polymorphisms with obesity-related phenotypes in European adolescents, and the influence of physical activity on these relationships. Methods Five polymorphisms of PTPN1 were genotyped in 1,057 European adolescents (12–18 years old). We measured several phenotypes related to obesity, such as adiposity markers, and biochemical and clinical parameters. Physical activity was objectively measured by accelerometry. Results The T, A, T, T and G alleles of the rs6067472, rs10485614, rs2143511, rs6020608 and rs968701 polymorphisms, respectively, were associated with lower levels of obesity-related phenotypes (i.e., body mass index, body fat percentage, hip circumference, fat mass index, systolic blood pressure and leptin) in European adolescents. In addition, the TATTG haplotype was associated with lower body fat percentage and fat mass index compared to the AACCA haplotype. Finally, when physical activity levels were considered, alleles of the rs6067472, rs2143511, rs6020608 and rs968701 polymorphisms were only associated with lower adiposity in active adolescents. Conclusions PTPN1 polymorphisms were associated with adiposity in European adolescents. Specifically, alleles of these polymorphisms were associated with lower adiposity only in physically active adolescents. Therefore, meeting the recommendations of daily physical activity may reduce obesity risk by modulating the genetic predisposition to obesity.European Commission FOOD-CT-2005-007034Marie S. Curie Global Fellowship within the European Union research and innovation framework programme (2014-2020; ClimAHealth)Ministry of Science and Innovation, Spain (MICINN) Spanish Government AGL2007-29784-ERedes Tematicas de Investigacion Cooperativa RETIC grant Red SAMID RD16/0022University of Granada Plan Propio de Investigacion (Excellence actions: Unit of Excellence on Exercise and Health [UCEES])Junta de Andalucia P18-624 RT-4455 SOMM17/6107/UGRPublic University of Navarr

H3K18 lactylation marks tissue‑specific active enhancers

Background: Histone lactylation has been recently described as a novel histone posttranslational modification linking cellular metabolism to epigenetic regulation. Results: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG islandcontaining promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue. Conclusions: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.ETH Zurich ETH Zurich core fundingEuropean Research Council (ERC) European Commission 803491Botnar Research Centre for Child Health Multi-Investigator ProjectWorld Food System Center of ETH ZurichIntegrative Food and Nutrition Center of EPF

La condició física com a determinant de salut en persones joves

La pràctica d’activitat física és un dels hàbits saludables més recomanats per nombrosos experts. D’altra banda, el començament dels estudis universitaris coincideix, en molts casos, amb l’inici del sedentarisme. En aquest estudi pretenem de conèixer i analitzar els hàbits de pràctica esportiva i relacionar-los amb els estils de vida de l’alumnat de la Universitat de Huelva. Per obtenir dades d’aquesta població d’estudi hem disse­nyat un qüestionari que recull aspectes com ara: dades identificatives, gestió esportiva universitària, pràctica d’activitat física, aspectes psicosocials de la pràctica d’activitat fisicoesportiva, influència de l’educació física escolar, temps lliure, i hàbits saludables. Per al disseny d’aquest instrument hem utilitzat una tècnica de consulta a experts anomenada mètode Delphi. Abans d’administrar-lo a tota la Universitat, per tal d’assegurar-ne la validesa, vam realitzar un estudi pilot a la Facultat de Ciències de l’Educació. Un cop corregit es va aplicar a la mostra representativa dels universitaris. Posteriorment, amb la finalitat d’aprofundir sobre aquestes dades, es van dissenyar i es van aplicar unes entrevistes en forma d’històries de vida a quatre alumnes amb diferents perfils, per tal d’ampliar la informació sobre els seus hàbits de pràctica d’activitat física. A continuació, es van comparar les dades obtingudes amb tots dos instruments. Entre els resultats obtinguts del qüestionari podem destacar que, el 41,9 % de l’alumnat practica activitat física, encara que amb una freqüència d’almenys tres dies per setmana es redueix al 23,7 %; els homes són més actius que les dones. Els que practiquen activitat física tenen millor autopercepció de la pròpia salut, organitzen millor el seu temps lliure, i tenen millors hàbits d’alimentació. Quant a la forma de pràctica, prefereixen realitzar activitat física no reglada, i acompanyats, principalment pels amics. Els alumnes que treballen i els que tenen més diners són més actius. L’abandonament de la pràctica d’activitat física coincideix amb l’entrada a la Universitat. El motiu principal pel qual abandonen o pel qual no practiquen és per no tenir temps. D’altra banda, la raó més important per la qual realitzen activitat física és “per fer exercici”. Les alumnes entrevistades coincideixen en els resultats obtinguts del qüestionari, però permeten d’aprofundir en les circumstàncies que han envoltat la seva vida en els moments clau en què han practicat o no activitat física. A tall d’exemple podem destacar la influència que la família ha tingut sobre elles, perquè practiquin o no practiquin activitat física. Finalment, amb aquestes dades hem plantejat un seguit d’implicacions amb què es podrien millorar els hàbits de pràctica d’activitat física de l’alumnat universitari

La condición física como determinante de salud en personas jóvenes

Conocer la relación entre capacidad aeróbica, fuerza muscular y factores de riesgo de enfermedad cardiovascular en niños y adolescentes es de interés científico y sanitario. Además, para poder interpretar de una manera más precisa estas asociaciones es necesario disponer de una metodología sencilla y fiable. Esto puede ayudar a crear estrategias de prevención primaria desde las edades más tempranas. El objetivo general de esta memoria de Tesis Doctoral es estudiar la relación entre condición física (especialmente capacidad aeróbica y fuerza muscular) y factores de riesgo de enfermedad cardiovascular en jóvenes, así como desarrollar nuevos métodos de estimación de la capacidad aeróbica y fuerza muscular en adolescentes. Un total de 873 niños de 9 a 10 años y 971 adolescentes de 12 a 19 años conforman las poblaciones que han participado en los tres estudios de cohortes incluidos en la presente memoria de Tesis: El estudio AVENA (Alimentación y Valoración del Estado Nutricional de los Adolescentes Españoles), el EYHS (European Youth Heart Study), y el estudio HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence). Los principales resultados de la memoria de Tesis sugieren que: a) La condición física se relaciona con parámetros de salud en niños y adolescentes. b) La capacidad aeróbica se asocia inversamente con factores tradicionales de enfermedad cardiovascular en niños de 9 a 10 años. c) La capacidad aeróbica se asocia con un factor novel de enfermedad cardiovascular tal como la homocisteína en niñas adolescentes, y esto tras ajustar por distintas variables de confusión incluido el genotipo MTHFR 677C&gt;T. d) La fuerza muscular se asocia a proteínas de inflamación aguda tales como la proteína C reactiva en adolescentes. e) Se ha desarrollado y validado una nueva fórmula de estimación del consumo máximo de oxígeno a partir del resultado obtenido en el test de ida y vuelta de 20 metros, el sexo, la edad, el peso y la talla del adolescente. f) Hay un tamaño de agarre óptimo que debería ser ajustado en el dinamómetro cuando se evalúe la fuerza de prensión manual en adolescentes. Los resultados de la presente memoria de Tesis muestran que la condición física en general y la capacidad aeróbica y la fuerza muscular en particular constituyen un importante marcador de salud en jóvenes, al igual que ya se había mostrado en adultos. Estos datos confirman la necesidad de incluir este tipo de mediciones en los sistemas educativos y de salud pública. El desarrollo de nuevos métodos de evaluación de la condición física para ser aplicados en estudios epidemiológicos ayudará a mejorar la calidad y el rigor de los mismos

Effects of exercise in addition to a family-based lifestyle intervention program on hepatic fat in children with overweight

ClinicalTrials.gov ID: NCT02258126Background: Paediatric hepatic steatosis is highly prevalent and closely related to type 2 diabetes. Aims: To determine whether the addition of supervised exercise to a family-based lifestyle- and psycho-educational intervention results in greater reduction of percentage hepatic fat (HF), adiposity, and cardiometabolic risk factors in children with overweight/obesity. Methods: The study subjects of this non-randomized, two-arm, parallel design, clinical trial were 116 overweight/obese children (10.6±1.1 years, 53.4% girls) living in Vitoria-Gasteiz (Spain). For 22 weeks they followed either a lifestyle- and psycho-education program (control intervention [CI], N=57), consisting of two family-based education sessions/month, or the same plus supervised exercise (intensive intervention [II], N=59) focused mainly on high-intensity aerobic workouts (3 sessions/week, 90 min/session). The primary outcome was the change in percentage HF (as measured by MRI) between baseline and the end of the intervention period. Secondary outcomes included changes in body mass index (BMI), fat mass index (FMI), abdominal fat (measured by dual-X-ray-absorptiometry), blood pressure, triglycerides, high density lipoprotein, low density lipoprotein, gamma-glutammyl-transferase, glucose and insulin concentrations. Results: A total of 102 children completed the trial (N=53 and N=49 in the CI and II groups, respectively). Percentage HF decreased only in the II group (-1.20±0.31% vs. 0.04±0.30%, II and CI, respectively), regardless of baseline value and any change in adiposity (P<0.01). BMI, FMI, abdominal fat (P≤0.001) and insulin (P<0.05) were reduced in both groups. Conclusions: Multicomponent intervention programs that include exercise training may help reduce, adiposity, insulin resistance and hepatic steatosis in overweight/obese children.Spanish Ministry of Health "Fondos de Investigation Sanitaria del Institute de Salud Carlos III" PI13/01335Spanish Ministry of Industry and Competitiveness DEP2016-78377-REU Fondos Estructurales de la Union Europea (FEDER) funds ("Una manera de hacer Europa")Spanish Ministry of Education, Culture and Sports FPU14/03329Education Department of the Government of the Basque Country PRE_2016_1_0057 PRE_2017_2_0224 PRE_2018_2_0057University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (FEDER) SOMM17/6107/UG

Validez y fiabilidad del test de correr-caminar 1/4 de milla en niños y adolescentes físicamente activos

We investigated the criterion-related validity and the reliability of the 1/4 mile run-walk test (MRWT) in children and adolescents. A total of 86 children (n=42 girls) completed a maximal graded treadmill test using a gas analyzer and the 1/4MRW test. We investigated the test-retest reliability of the 1/4MRWT in a different group of children and adolescents (n=995, n=418 girls). The 1/4MRWT time, sex, and BMI significantly contributed to predict measured VO2peak (R2= 0.32). There was no systematic bias in the cross-validation group (P>0.1). The root mean sum of squared errors (RMSE) and the percentage error were 6.9 ml/kg/min and 17.7%, respectively, and the accurate prediction (i.e. the percentage of estimations within ±4.5 ml/kg/min of VO2peak) was 48.8%. The reliability analysis showed that the mean inter-trial difference ranged from 0.6 seconds in children aged 6-11 years to 1.3 seconds in adolescents aged 12-17 years (all P<0.001). In conclusion, the present study shows that the criterion-related validity of the 1/4MRW test is relatively low in the sample of children and adolescents studied. Beside the statistical significance, the reliability of the 1/4MRWT was considered acceptable, i.e. mean difference between tests ranged from half second to one second.El objetivo del presente estudio fue analizar la validez de criterio y la fiabilidad del test de correr-caminar 1/4 de milla en jóvenes. Participaron un total de 86 jóvenes (42 niñas). Los participantes realizaron un test máximo en tapiz rodante para determinar el consumo de oxígeno pico (VO2pico), así como el test de correr-caminar 1/4 de milla. La fiabilidad test-retest se estudió en un grupo distinto de jóvenes (n=995, n=418 niñas). El tiemplo empleado en realizar el test de correr-caminar 1/4 de milla, el sexo, y el índice de masa corporal contribuyeron de forma significativa a predecir el VO2pico (R2= 0.32). No se observó diferencia sistemática en el grupo de cross-validación (P>0.1). La suma de los errores al cuadrado fue de 6.9 ml/kg/min y el porcentaje de error fue del 17.7%. El porcentaje de estimaciones entre un ±4.5 ml/kg/min del VO2pico fue del 58.8%. El análisis de fiabilidad mostró que la diferencia entre test osciló entre 0.6 segundos en niños de 6-11 años a 1.3 segundo en adolescentes de 12-17 años (todos P<0.001). En conclusión, el presente estudio muestra que la validez de criterio del test de correr-caminar 1/4 de milla es baja en los jóvenes estudiados. La fiabilidad fue sin embargo aceptable.The study was funded by Centro Andaluz de Medicina del Deporte, Junta de Andalucía, Orden 4/02/05, BOJA nº 37 (Ref. JA-CTD2005-01) and the Spanish Ministry of Science and Innovation (RYC-2010-05957, RYC-2011-09011)

Effects of a Family-Based Lifestyle Intervention Plus Supervised Exercise Training on Abdominal Fat Depots in Children With Overweight or Obesity. A Secondary Analysis of a Nonrandomized Clinical Trial

IMPORTANCE Excess abdominal fat is a major determinant in the development of insulin resistance and other metabolic disorders. Increased visceral adipose tissue (VAT) seems to precede the development of insulin resistance and is therefore a prime target of childhood lifestyle interventions aimed at preventing diabetes. OBJECTIVES To examine the effect of added exercise to a family-based lifestyle intervention program designed to reduce VAT plus subcutaneous (ASAT), intermuscular (IMAAT), and pancreatic (PAT) adipose tissue in children with overweight or obesity and to explore the effect of changes in VAT on insulin resistance. DESIGN, SETTING, AND PARTICIPANTS This 2-group, parallel-design clinical trial was conducted in Vitoria-Gasteiz, Spain. A total of 116 children with overweight or obesity participated and were assigned to a 22-week family-based lifestyle program (control group [n = 57]) or the same program plus an exercise intervention (exercise group [n = 59]). Data were collected between September 1, 2014, and June 30, 2017, and imaging processing for fat depot assessments and data analysis were performed between May 1, 2019, and February 12, 2021. INTERVENTIONS The compared interventions consisted of a family-based lifestyle and psychoeducation program (two 90-minute sessions per month) and the same program plus supervised exercise (three 90-minute sessions per week). MAIN OUTCOMES AND MEASURES The primary outcome of this study was the change in VAT between baseline and 22 weeks as estimated by magnetic resonance imaging. The secondary outcomes were changes in ASAT, IMAAT, and PAT. The effect of changes in VAT area on insulin resistance was also recorded. RESULTS The 116 participants included in the analysis (62 girls [53.4%]) had a mean (SD) age of 10.6 (1.1) years, and 67 (57.8%) presented with obesity. Significantly greater reductionswere recorded for the exercise group in terms of reduction in VAT (−18.1%vs −8.5%for the control group; P = .004), ASAT (−9.9%vs −3.0%; P = .001), and IMAAT (−6.0%vs −2.6%; P = .02) fat fractions compared with the control group. Changes in VAT explained 87.6%of the improvement seen in insulin resistance (β = −0.102 [95%CI, −0.230 to −0.002]). CONCLUSIONS AND RELEVANCE These findings suggest that the addition of exercise to a lifestyle intervention program substantially enhanced the positive effects on abdominal fat depots in children with overweight or obesity. In addition, the reduction in VAT seemed to largely mediate the improvement of insulin sensitivity. These results highlight the importance of including exercise as part of lifestyle therapies aimed at treating childhood obesity and preventing the development of type 2 diabetes.Spanish Ministry of Health's Fondos de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01335 Spanish Government DEP2016-78377European Commission 0011-1365-2019-000085Regional Government of Navarra's Department of Economic Development - ERDF Government of Navarra's Department of Health 47/2021Ministry of Science and Innovation, Spain (MICINN) Spanish Government FJC2018-037925-IMarie Sklodowska Curie 101028929 European CommissionEducation Department of the Government of the Basque Country BES-2017-080770 PRE_2016_1_0057 PRE_2017_2_0224 PRE_2018_2_0057 PRE_2019_2_0004Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades, ERDF SOMM17/6107/UG

Estudio de una linea automática de ensamblado de bidones para ciclistas de 550ml

En el presente Trabajo de Final de Grado se pretende hacer el estudio de una línea automática para el ensamblaje de un bidón de bicicletas de 550ml. Primeramente, se analizará el producto a ensamblar, materiales, zonas de contacto y especificaciones que el fabricante nos marque para, posteriormente, poder diseñar la línea. Se realizará un diseño de tipo conceptual que contenga la maquinaria que se requiera para desarrollar el ciclo de trabajo, así como los útiles y elementos estructurales necesarios para ello. En éste podremos ver diferentes soluciones para distintas aplicaciones y el criterio seguido para su elección. Seguidamente se calcularán los tiempos que van a afectar en la línea y que se deberán tener en cuenta para calcular la producción. Finalmente se comentarán aspectos del lado de la seguridad, aunque no es el objetivo de este trabajo final de grado

Physical activity, overweight and central adiposity in Swedish children and adolescents: the European Youth Heart Study

BACKGROUND: The aim of this work was to study the associations of physical activity (PA) and other factors predisposing to overweight, with overweight and central adiposity in children and adolescents. METHODS: A total of 557 Swedish children (9.5 +/- 0.3 y) and 517 adolescents (15.6 +/- 0.4 y) from the European Youth Heart Study participated in this study. Logistic regression analyses were used to examine the associations of PA, as measured by accelerometry, and other determinants (i.e. television viewing, birth weight, maternal educational level and parental overweight) with total and central adiposity. Body mass index and waist circumference cut-off values proposed by the IOTF and the Bogalusa Heart Study (i.e. waist measures for predicting risk factors clustering, hereinafter called high-risk waist circumference), respectively, were used. Fatness was estimated from skinfold thicknesses and dichotomized using the 85th sex- and age-specific percentile (high/low). RESULTS: Children and adolescents who had a low level (first tertile) of vigorous PA, were more likely to be overweight (including obesity) and to have a high-risk waist circumference, than those with a high level (third tertile) of vigorous PA. Similarly, those subjects who had a low or middle level (second tertile) of total PA were more likely to be overweight than those who had a high level of total PA. Among the PA variables, only vigorous PA was associated with high total fatness. Birth weight and television viewing, were also associated with higher odds of having a high-risk waist circumference, but these associations were attenuated once either total or vigorous PA variable was included in the model. Those subjects who had two overweight parents were more likely to be overweight and to have a high-risk waist circumference independently of PA variables, compared to those whose parents were not overweight. CONCLUSION: Low levels of total PA and especially vigorous PA may play an important role in the development of overweight and excess of central adiposity in children and adolescents, independently of a number of factors such as television viewing and birth weight. In addition, the data suggest that the association between television viewing and central fat deposition could be attenuated if enough vigorous PA is accumulated. Longitudinal and intervention studies are needed to confirm these findings.This study was supported by grants from the Stockholm County Council. FBO and JRR were supported by grants from the Consejo Superior de Deportes (109/UPB31/03, 13/UPB20/04), Ministerio de Educación y Ciencia de España (AP2003-2128, AP2004-2745), EU DG Sanco, project ALPHA (2006120), and the Margit and Folke Pehrzon Foundation