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

Author

Anguita-Ruiz, Augusto, Bustos-Aibar, Mireia, Plaza-Díaz, Julio, Mendez-Gutierrez, Andrea, Alcalá-Fdez, Jesús, Aguilera, Concepción María, Ruiz-Ojeda, Francisco Javier, [Anguita-Ruiz,A, Bustos-Aibar,M, Plaza-Díaz,J, Mendez-Gutierrez,A, Aguilera,CM, Ruiz-Ojeda,FJ] Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain. [Anguita-Ruiz,A, Ruiz-Ojeda,FJ] Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, Madrid, Spain. [Plaza-Díaz,J] Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada. [Alcalá-Fdez,J] Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain. [Ruiz-Ojeda,FJ] RG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, Neuherberg, Munich, Germany., and AMG is supported by a doctorate fellowship Formación del Profesorado Universitario (FPU 16/03653)', which is being completed as part of the Nutrition and Food Sciences Program at the University of Granada, Spain. AAR is supported by a doctorate contract i-PFIS: Doctorados IIS-empresa en ciencias y tecnologías de la salud (IFI17/00048). JPD is supported by a grant to postdoctoral researchers at foreign Universities and Research Centers from the 'Ramón-Areces Foundation', Spain. FJRO is part of the 'Personal Investigador Doctor', University of Granada, funded by Junta de Andalucía (PAIDI, 2020).

Subjects
Anatomy::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix [Medical Subject Headings], Tejido adiposo, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies::Genome-Wide Association Study [Medical Subject Headings], Obesidad, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Adipose tissue, Skeletal muscle, Epigenetic, Anatomy::Musculoskeletal System::Muscles::Muscle, Skeletal [Medical Subject Headings], Extracellular matrix, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases [Medical Subject Headings], Genética, Músculo esquelético, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Transcriptoma, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription, Genetic::Transcriptome [Medical Subject Headings], Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White [Medical Subject Headings], Transcriptomic, Epigenómica, Genetics, Organisms::Eukaryota::Animals [Medical Subject Headings], Obesity, Matriz extracelular
Abstract

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. Yes

Published
2021

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

Author

María D. Mesa, Rosaura Leis, Augusto Anguita-Ruiz, Azahara I. Rupérez, Concepción M. Aguilera, Luis A. Moreno, Angel Gil, Francisco Jesus Llorente-Cantarero, Francisco Javier Aguilar-Gómez, Gloria Bueno, Rocío Vázquez-Cobela, Mercedes Gil-Campos, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Llorente-Cantarero,FJ] Department of Specific Didactics, Faculty of Education, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ, Leis,R, Bueno,G, Anguita-Ruiz,A, Vázquez-Cobela,R, Moreno,LA, Gil,A, Aguilera,CM, Gil-Campos,M] CIBEROBN, (Physiopathology of Obesity and Nutrition) Institute of Health Carlos III (ISCIII), Madrid, Spain. [Aguilar-Gomez FJ, Gil-Campos,M] Metabolism and Investigation Unit, Reina Sofía University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Leis,R, Vázquez-Cobela,R] Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, University of Santiago de Compostela, Clinic University Hospital of Santiago, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain. [Bueno,G] Pediatric Endocrinology Unit, Clinic University Hospital Lozano Blesa, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain. [Bueno,G, Rupérez,AI, Moreno,LA] GENUD Research Group, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Zaragoza, Spain. [Anguita-Ruiz,A, Mesa,MA, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs Granada, 18014 Granada, Spain., This research was funded by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/02042, PI11/02059, PI11/01425, and PI16/00871, PI16/01301, PI16/01205) and RETIC (Redes temáticas de investigación cooperativa) (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding of A.A.R: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). Á.G. was funded by the Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spain This paper will be included in F.J.A. doctorate, under the 'Biomedicine Program' at the University of Córdoba, Spain.

Subjects
Antioxidant, Isoprostane, 8-hydroxy-2′-deoxyguanosine, Physiology, medicine.medical_treatment, Clinical Biochemistry, Physical fitness, physical activity, medicine.disease_cause, Biochemistry, Acelerometría, chemistry.chemical_compound, 0302 clinical medicine, Accelerometry, oxidative stress, 030212 general & internal medicine, Isoprostane F2α, Plasma total antioxidant capacity, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Health Care::Health Care Economics and Organizations::Organizations::International Agencies::United Nations::World Health Organization [Medical Subject Headings], Total plasma, plasma total antioxidant capacity, Estrés oxidativo, Ejercicio físico, isoprostane F2, Antioxidant capacity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Titrimetry::Colorimetry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent Assay [Medical Subject Headings], 8-Hidroxi-2'-Desoxicoguanosina, medicine.medical_specialty, Physical activity, Article, 03 medical and health sciences, Internal medicine, isoprostane F2α, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Antioxidants [Medical Subject Headings], medicine, accelerometry, Pysical activity, Molecular Biology, Redox homeostasis, business.industry, lcsh:RM1-950, 030229 sport sciences, Cell Biology, 8-hydroxy-20-deoxyguanosine, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Physical Fitness [Medical Subject Headings], lcsh:Therapeutics. Pharmacology, chemistry, Oxidative stress, business
Abstract

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-20-deoxyguanosine (8-OHdG) and isoprostane F2 (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., Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI11/02042 PI11/02059 PI11/01425 PI16/00871 PI16/01301 PI16/01205, RETIC (Redes temáticas de investigación cooperativa) Red SAMID RD12/0026/0015, Instituto de Salud Carlos III European Commission IFI17/00048, Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spain

Published
2021

3. Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies

Author

Anguita-Ruiz, Augusto, Aguilera, Concepción M., Gil, Ángel, [Anguita-Ruiz,A, Aguilera,CM, Gil,Á] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Armilla, Granada, Spain. [Anguita-Ruiz,A, Gil,Á] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Anguita-Ruiz,A, Gil,Á] CIBEROBN (Physiopathology of Obesity and Nutrition Network CB12/03/30038), Institute of Health Carlos III (ISCIII), Madrid, Spain., and This research was supported by the Bionit group (CTS461) funded by the Andalusian Plan of Research, development and innovation (PAIDI). The authors also acknowledge Instituto de Salud Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048).

Subjects
Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Lactose intolerance, Lactase-phlorizin hydrolase, Intolerancia a la lactosa, Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Malabsorption Syndromes::Lactose Intolerance [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Glycoside Hydrolases::Galactosidases::beta-Galactosidase::Lactase [Medical Subject Headings], Genética, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings], Phenomena and Processes::Biological Phenomena::Biological Processes::Biological Evolution::Evolution, Molecular [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Dairy Products::Milk [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Lactase persistence, Epigenómica, Genetics, Organisms::Eukaryota::Animals [Medical Subject Headings], Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Glycoside Hydrolases::Galactosidases::beta-Galactosidase::Lactase::Lactase-Phlorizin Hydrolase [Medical Subject Headings], Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::Lactose [Medical Subject Headings], Epigenetics, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Lactasa, Lactasa-florizina hidrolasa, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Lactase non-persistence, Lactase
Abstract

In humans the ability to digest milk lactose is conferred by a β-galactosidase enzyme called lactase-phlorizin hydrolase (LPH). While in some humans (approximately two-thirds of humankind) the levels of this enzyme decline drastically after the weaning phase (a trait known as lactase non-persistence (LNP)), some other individuals are capable of maintaining high levels of LPH lifelong (lactase persistence (LP)), thus being able to digest milk during adulthood. Both lactase phenotypes in humans present a complex genetic basis and have been widely investigated during the last decades. The distribution of lactase phenotypes and their associated single nucleotide polymorphisms (SNPs) across human populations has also been extensively studied, though not recently reviewed. All available information has always been presented in the form of static world maps or large dimension tables, so that it would benefit from the newly available visualization tools, such as interactive world maps. Taking all this into consideration, the aims of the present review were: (1) to gather and summarize all available information on LNP and LP genetic mechanisms and evolutionary adaptation theories, and (2) to create online interactive world maps, including all LP phenotype and genotype frequency data reported to date. As a result, we have created two online interactive resources, which constitute an upgrade over previously published static world maps, and allow users a personalized data exploration, while at the same time accessing complete reports by population or ethnicity. Yes

Published
2020

4. eXplainable Artificial Intelligence (XAI) for the identification of biologically relevant gene expression patterns in longitudinal human studies, insights from obesity research

Author

Jesús Alcalá-Fdez, Augusto Anguita-Ruiz, Concepción M. Aguilera, Rafael Alcalá, Alberto Segura-Delgado, [Anguita-Ruiz,A, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'Jose´ Mataix', Center of Biomedical Research, University of Granada, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigacio´n Biosanitaria ibs.GRANADA, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] CIBEROBN (Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Segura-Delgado,A, Alcalá,R, Alcalá-Fdez,J] Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain., and This work was supported by the Mapfre Foundation ('Research grants by Ignacio H. de Larramendi 2017') and by the Regional Government of Andalusia ('Plan Andaluz de investigación, desarrollo e innovación (2018), P18- RT-2248'). The authors also acknowledge the Institute of Health Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016, Project number: IFI17/00048.

Subjects
0301 basic medicine, Information Science::Information Science::Medical Informatics::Medical Informatics Applications::Information Storage and Retrieval::Data Mining [Medical Subject Headings], Computer science, Microarrays, Physiology, Gene regulatory network, Obesidad, Gene Expression, Information Science::Information Science::Medical Informatics::Medical Informatics Applications::Information Systems::Databases as Topic::Databases, Factual::Databases, Genetic [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Machine Learning, Database and Informatics Methods, 0302 clinical medicine, Software, Information Science::Information Science::Computing Methodologies::Artificial Intelligence [Medical Subject Headings], Information Science::Information Science::Computing Methodologies::Software [Medical Subject Headings], Databases, Genetic, Medicine and Health Sciences, Data Mining, Gene Regulatory Networks, Longitudinal Studies, Biology (General), Soundness, Functional validation, Ecology, Human studies, Phenomena and Processes::Genetic Phenomena::Genetic Processes [Medical Subject Headings], Applied Mathematics, Simulation and Modeling, Inteligencia artificial, Identification (information), Knowledge, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Transcriptome [Medical Subject Headings], Bioassays and Physiological Analysis, Computational Theory and Mathematics, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology [Medical Subject Headings], Physiological Parameters, Modeling and Simulation, Physical Sciences, Information Technology, Sequence Analysis, Algorithms, Research Article, Computer and Information Sciences, Process (engineering), Bioinformatics, QH301-705.5, Sequence Databases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], Minería de datos, Research and Analysis Methods, Mining, 03 medical and health sciences, Cellular and Molecular Neuroscience, Conocimiento, Artificial Intelligence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies [Medical Subject Headings], Genetics, Humans, Gene Regulation, Obesity, Molecular Biology, Ecology, Evolution, Behavior and Systematics, business.industry, Gene Expression Profiling, Body Weight, Biology and Life Sciences, Computational Biology, Pipeline (software), Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Transcriptoma, 030104 developmental biology, Biological Databases, Artificial intelligence, Gene expression, business, Information Science::Information Science::Computing Methodologies::Algorithms [Medical Subject Headings], Transcriptome, 030217 neurology & neurosurgery, Mathematics, Expresión génica
Abstract

Until date, several machine learning approaches have been proposed for the dynamic modeling of temporal omics data. Although they have yielded impressive results in terms of model accuracy and predictive ability, most of these applications are based on “Black-box” algorithms and more interpretable models have been claimed by the research community. The recent eXplainable Artificial Intelligence (XAI) revolution offers a solution for this issue, were rule-based approaches are highly suitable for explanatory purposes. The further integration of the data mining process along with functional-annotation and pathway analyses is an additional way towards more explanatory and biologically soundness models. In this paper, we present a novel rule-based XAI strategy (including pre-processing, knowledge-extraction and functional validation) for finding biologically relevant sequential patterns from longitudinal human gene expression data (GED). To illustrate the performance of our pipeline, we work on in vivo temporal GED collected within the course of a long-term dietary intervention in 57 subjects with obesity (GSE77962). As validation populations, we employ three independent datasets following the same experimental design. As a result, we validate primarily extracted gene patterns and prove the goodness of our strategy for the mining of biologically relevant gene-gene temporal relations. Our whole pipeline has been gathered under open-source software and could be easily extended to other human temporal GED applications., Author summary Biological processes in humans are not single-gene based mechanisms, but complex systems controlled by regulatory interactions between thousands of genes. Within these gene regulatory networks, time-delay is a common phenomenon and genes interact each other within a four-dimension space. Hence, to fully understand or to control biological processes we need to unravel the principles of gene-gene temporal interactions. Until date, several approaches based on Artificial Intelligence methods have tried to address this issue. Nevertheless, the research community has claimed for more interpretable and biologically meaningful models. Particularly, scientists claim for methods able to infer gene-gene temporal interactions that could be later validated with real-life experiments at the lab. The recent revolution known as “eXplainable Artificial Intelligence” offers a solution for this issue, where a range of highly interpretable and explicable models has become available. Many of these methods could be applied to temporal gene expression data in order to decipher mentioned temporal gene-gene relationships in humans. Here, we propose and validate a new pipeline analysis including an eXplainable artificial intelligence method for the identification of comprehensible gene-gene temporal relationships from human intervention studies. Our method has been validated in six datasets from obesity research (consisting of low calorie diets interventions), where it was able to extract meaningful gene-gene temporal interactions with relevance the etiology of the disease. The application of our pipeline to other type of human temporal gene profiles would greatly expand our knowledge for complex biological processes, with a special interest for drug clinical trials, in which identified gene-gene regulatory interactions could reveal new therapeutic targets.

Published
2020

5. Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty

Author

Luis A. Moreno, Rosaura Leis, Jesús Alcalá-Fdez, Augusto Anguita-Ruiz, Francisco Jesus Llorente-Cantarero, Azahara I. Rupérez, Concepción M. Aguilera, Gloria Bueno, Esther M González-Gil, Angel Gil, Belén Pastor-Villaescusa, Mercedes Gil-Campos, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Anguita-Ruiz,A, González-Gil,EM, Pastor-Villaescusa,B, Gil,Á, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Anguita-Ruiz,A, Llorente-Cantarero,FJ, Moreno,LA, Gil-Campos,M, Bueno,G, Leis,R, Aguilera,CM] CIBEROBN (Physiopathology of Obesity and Nutrition Network CB12/03/30038), Institute of Health Carlos III (ISCIII), Madrid, Spain. [González-Gil,EM, Rupérez,AI, Bueno,G] Growth, Exercise, Nutrition and Development (GENUD) Research Group, Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain. [Llorente-Cantarero,FJ] Department of Specific Didactics, Faculty of Education, University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ, Gil-Campos,M] PAIDI CTS-329, Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain. [Pastor-Villaescusa,B] LMU—Ludwig-Maximilians-University of Munich, Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, University of Munich Medical Center, Munich, Germany. [Alcalá-Fdez,J] Department of Computer Science and Artificial Intelligence, University of Granada,Granada, Spain. [Gil-Campos,M] Unit of Pediatric Endocrinology, Reina Sofia University Hospital, Córdoba, Spain. [Bueno,G] Pediatric Department, Lozano Blesa University Clinical Hospital, University of Zaragoza, Zaragoza, Spain. [Leis,R] Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, Spain., This research was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI1102042, PI1102059, PI1601301 and PI1600871), by the Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products (EC10-243, EC10-056, EC10-281 and EC10-227), and by the Regional Government of Andalusia ('Plan Andaluz de investigación, desarrollo e innovación (2018), P18-RT-2248') and by the Mapfre Foundation ('Research grants by Ignacio H. de Larramendi 2017'). The authors also acknowledge Instituto de Salud Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). The authors also acknowledge the University of Granada 'Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)'.

Subjects
Síndrome metabólico, obesity, puberty, Pediatrics, Obesidad, Gene-environment interactions, lcsh:Medicine, Spanish children, Disease, Predictive ability, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], 0302 clinical medicine, genetics, 030212 general & internal medicine, Childhood obesity, Pubertad, pharmacogenetics, 0303 health sciences, Farmacogenética, gene-environment interactions, General Medicine, Metabolic syndrome, Genetic risk score, Metformin, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::Metformin [Medical Subject Headings], Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Pharmacogenetics [Medical Subject Headings], childhood obesity, medicine.drug, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Puberty [Medical Subject Headings], genetic risk score, Article, metabolic syndrome, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], 03 medical and health sciences, Obesidad pediátrica, medicine, Genetic predisposition, Genetics, Persons::Persons::Age Groups::Child [Medical Subject Headings], Obesity, Interacción gen-ambiente, Persons::Persons::Age Groups::Adult [Medical Subject Headings], childhood, 030304 developmental biology, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, lcsh:R, Puberty, predictive ability, medicine.disease, Genética, Childhood, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity::Pediatric Obesity [Medical Subject Headings], Pharmacogenetics, business, Body mass index
Abstract

The authors would like to thank the Spanish children and parents who participated in the study., Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic variants have been widely associated with obesity in children populations. The implication of such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the prediction and pharmacological management of obesity in Spanish children, further investigating its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted on genetics data from three well-characterized children populations (composed of 574, 96 and 124 individuals), following both cross-sectional and longitudinal designs, expanding childhood and puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI Z-Score (B = 1.56, SE = 0.27 and p-value = 1.90 × 10−8 ), and that could be used as a good predictor of obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not associated with cardio-metabolic comorbidities in children and that certain environmental factors interact with the genetic predisposition to the disease. Finally, according to the results derived from a weight-reduction metformin intervention in children with obesity, we discarded the utility of the pGRS as a pharmacogenetics marker of metformin response., Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI1102042 PI1102059 PI1601301 PI1600871, Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products EC10-243 EC10-056 EC10-281 EC10-227, Regional Government of Andalusia ("Plan Andaluz de investigacion, desarrollo e innovacion (2018)") P18-RT-2248, Mapfre Foundation ("Research grants by Ignacio H. de Larramendi 2017"), Instituto de Salud Carlos III IFI17/00048

Published
2020

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

Author

Gloria Bueno, Francisco Jesus Llorente-Cantarero, Concepción M. Aguilera, Juan Jose Bedoya-Carpente, Augusto Anguita-Ruiz, Mercedes Gil-Campos, Jose Manuel Jurado-Castro, Rosaura Leis, Azahara Iris-Rupérez, Rocío Vázquez-Cobela, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Leis,R, Bedoya-Carpente,JJ, Vázquez-Cobela,R] Unidad de Investigación en Nutrición, Crecimiento y Desarrollo Humano de Galicia, Departamento de Pediatría, Hospital Clínico Universitario de Santiago, Universidad de Santiago de Compostela, IDIS, Santiago de Compostela, Spain. [Leis,R, Llorente-Cantarero,FJ, Anguita-Ruiz,A, Vázquez-Cobela,R, Aguilera,CM, Bueno,G, Gil-Campos,M] CIBEROBN, (Physiopathology of Obesity and Nutrition) Institute of Health Carlos III (ISCIII), Madrid, Spain. [Jurado-Castro,JM, Gil-Campos,M] Metabolism and Investigation Unit, Reina Sofia University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ] Department of Artistic and Corporal Education, Faculty of Education, University of Córdoba, Córdoba, Spain. [Anguita-Ruiz,A, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs, Granada, Spain. [Iris-Rupérez,A] GENUD Research Group, University of Zaragoza, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain. [Bueno,G] Unidad de Endocrinología Pediátrica, Hospital Clínico Lozano Blesa, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain., and This work was supported bythe Plan Nacional de Investigación Científica, Desarrollo e InnovaciónTecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI051968, PI1102042 and PI1600871) and Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding of A.A.-R: Contratos i-PFIS: doctorados IIS empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048).This paper will be included in J.M.J.-C. doctorate, under the 'Social and Legal Sciences Program' at theUniversity of Córdoba, Spain.

Subjects
Male, obesity, Mediterranean diet, Health Behavior, Obesidad, Child Behavior, Diet, Mediterranean, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Surveys and Questionnaires, Cluster Analysis, Insulin, 030212 general & internal medicine, skin and connective tissue diseases, Child, Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings], Nutrition and Dietetics, exercise, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Electrical Equipment and Supplies [Medical Subject Headings], Conducta sedentaria, Ejercicio físico, Cardiovascular diseases, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Child Behavior [Medical Subject Headings], Cohort, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Female, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Leisure Activities::Recreation::Sports [Medical Subject Headings], Club, Enfermedades cardiovasculares, lcsh:Nutrition. Foods and food supply, Sports, musculoskeletal diseases, Electrical Equipment and Supplies, Anatomy::Digestive System::Pancreas::Islets of Langerhans::Insulin-Secreting Cells [Medical Subject Headings], Physical activity, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, lcsh:TX341-641, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Cluster Analysis [Medical Subject Headings], Disease cluster, Article, Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], 03 medical and health sciences, Screen time, Environmental health, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], medicine, Humans, Persons::Persons::Age Groups::Child [Medical Subject Headings], Healthy Lifestyle, Obesity, Exercise, Triglycerides, business.industry, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Anthropometry, medicine.disease, Dieta mediterránea, cardiovascular diseases, stomatognathic diseases, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Sedentary Behavior, business, Food Science
Abstract

The authors would like to thank the children and parents who participated in the study and Ana Yara Postigo-Fuentes for the assistance with the English editing., 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., Plan Nacional de Investigacion Cientifica, Desarrollo e InnovacionTecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI051968 PI1102042 PI1600871, Redes tematicas de investigacion cooperativa RETIC (Red SAMID) RD12/0026/0015, Instituto de Salud Carlos III IFI17/00048

Published
2020

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