Abel Plaza-Florido1, Signe Altmäe2,3,4, Francisco J Esteban5, Cristina Cadenas-Sanchez6,7, Concepción M Aguilera4,8,9, Elisabet Einarsdottir10, Shintaro Katayama11,12, Kaarel Krjutškov3,12,13, Juha Kere11,12, Frank Zaldivar14, Shlomit Radom-Aizik14, Francisco B Ortega6,12. 1. PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, 18011, Granada, Spain. abeladrian@ugr.es. 2. Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada, Spain. 3. Competence Centre on Health Technologies, Tartu, Estonia. 4. Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. 5. Systems Biology Unit, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, Jaen, Spain. 6. PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, 18011, Granada, Spain. 7. Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Public University of Navarra, Pamplona, Spain. 8. Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Centre for Biomedical Research, University of Granada, Granada, Spain. 9. CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Madrid, Spain. 10. Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, SE-171 21, Solna, Sweden. 11. Stem Cells and Metabolism Research Program (STEMM), University of Helsinki, and Folkhälsan Research Center, Helsinki, Finland. 12. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. 13. Institute of Clinical Medicine, Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia. 14. Pediatric Exercise and Genomics Research Center, UC Irvine School of Medicine, Irvine, CA, USA.
Abstract
BACKGROUND: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes. The underlying mechanisms for those differences are still unclear. This study aimed to analyze the whole-blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. METHODS: Twenty-seven children with OW/OB (10.1 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein-cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers were additionally determined. Total blood RNA was analyzed by 5'-end RNA-sequencing. RESULTS: Whole-blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. Thirty-two genes differentially expressed were linked to metabolism, mitochondrial, and immune functions. CONCLUSIONS: The identified gene expression patterns related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity. IMPACT: A distinct pattern of whole-blood transcriptome profile (RNA-seq) was identified in children with metabolic healthy overweight/obesity (MHO) compared to metabolic unhealthy overweight/obesity (MUO) phenotype. The most relevant genes in understanding the molecular basis underlying the MHO/MUO phenotypes in children could be: RREB1, FAM83E, SLC44A1, NRG1, TMC5, CYP3A5, TRIM11, and ADAMTSL2. The identified whole-blood transcriptome profile related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.
BACKGROUND: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes. The underlying mechanisms for those differences are still unclear. This study aimed to analyze the whole-blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. METHODS: Twenty-seven children with OW/OB (10.1 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein-cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers were additionally determined. Total blood RNA was analyzed by 5'-end RNA-sequencing. RESULTS: Whole-blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. Thirty-two genes differentially expressed were linked to metabolism, mitochondrial, and immune functions. CONCLUSIONS: The identified gene expression patterns related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity. IMPACT: A distinct pattern of whole-blood transcriptome profile (RNA-seq) was identified in children with metabolic healthy overweight/obesity (MHO) compared to metabolic unhealthy overweight/obesity (MUO) phenotype. The most relevant genes in understanding the molecular basis underlying the MHO/MUO phenotypes in children could be: RREB1, FAM83E, SLC44A1, NRG1, TMC5, CYP3A5, TRIM11, and ADAMTSL2. The identified whole-blood transcriptome profile related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.
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