Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity Bustos Aibar, Mireia Aguilera García, Concepción María Alcalá Fernández, Jesús Ruiz Ojeda, Francisco Javier Plaza Díaz, Julio Plaza Florido, Abel Adrián Gacto Colorado, María José Anguita Ruiz, Augusto Childhood obesity Gene co-expression Hierarchical clustering Inter-tissue molecular signatures Skeletal muscle tissue Visceral adipose tissue Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesitymetabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (intertissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric population 2023-09-20T10:22:38Z 2023-09-20T10:22:38Z 2023-06-14 journal article M. Bustos-Aibar et al. Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity. Computers in Biology and Medicine 163 (2023) 107085[https://doi.org/10.1016/j.compbiomed.2023.107085] https://hdl.handle.net/10481/84522 10.1016/j.compbiomed.2023.107085 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier