ESPE2022 Poster Category 1 Fat, Metabolism and Obesity (73 abstracts)
1The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel; 2Physiology/Endocrinology, Institute of Neuroscience & Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark; 4Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 5School of Public Health, University of Haifa, Haifa, Israel; 6Pediatric Endocrinology, Haemek Medical Center, Haifa, Israel; 7Bioinformatics Knowledge Unit, The Lokey Center, Technion – Israel Institute of Technology, Haifa, Israel
Background/Aim: The trade-off theory claims that a resource (calorie) stored in adipose tissue cannot be used for longitudinal growth, and a calorie used for growth will not be stored as fat.
Methods: Out of 2339 children with longitudinal heights and weights (birth to adulthood) from the GrowUp1990 Gothenburg cohort, 1993 (996 girls) were analyzed. For everyone we calculated Energy Trade-Off Score: ETOS = at early adulthood. Four extreme body types were defined based on ETOS and Height: 135 individuals (78 girls) were tall-slender and 137 (77 girls) were short-stout (trade-off body types), while 127 (59 girls) were tall-stout and 146 (72 girls) were short-slender (non-trade-off body types). Genome Wide Association Studies (GWAS) using 362K individuals from the UK BioBank were conducted to identify SNPs associated with height, BMI, and ETOS. Results: and ETOS (unlike) trajectories in both trade-off groups showed a two-hit pattern with profound changes during early infancy and adolescent periods. In contrast, for the remaining groups their body type coalesced in childhood and changed little afterwards. Using GWAS, we identified 3258 SNPs out of ~11M gene variants in several loci (FTO, ADCY3, GDF5, among others) as being highly associated with ETOS. A subsequent pathway enrichment analysis discovered multiple pathways linked to ‘extracellular matrix organization’, ‘signal transduction’, ‘chromatin organization’, and ‘energy metabolism’.
Conclusion: ETOS represents a novel anthropometric trait of body build that highlights the spectrum between slender and stout. Multiple genomic loci and pathways are involved in energy trade-off that measured by ETOS.