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Bustos-Aibar, M.* ; Aguilera, C.M.* ; Alcalá-Fdez, J.* ; Ruiz Ojeda, F.J. ; Plaza-Díaz, J.* ; Plaza-Florido, A.* ; Tofe, I.* ; Gil-Campos, M.* ; Gacto, M.J.* ; Anguita-Ruiz, A.*

Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity.

Comput. Biol. Med. 163:107085 (2023)

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Open Access Green as soon as Postprint is submitted to ZB.

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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 obesity-metabolic 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 (inter-tissue, 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Childhood Obesity ; Gene Co-expression ; Hierarchical Clustering ; Inter-tissue Molecular Signatures ; Skeletal Muscle Tissue ; Visceral Adipose Tissue; Fatty Liver-disease; Insulin-resistance; Inflammation; Atherosclerosis; Overweight; Pathway; Nafld

ISSN (print) / ISBN 0010-4825

e-ISSN 1879-0534

Journal Computers in Biology and Medicine

Quellenangaben Volume: 163, Article Number: 107085

Publisher Elsevier

Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants ERDF/Health Institute Carlos III
ERDF/Regional Government of Andalusia/Ministry of Economic Transformation, Industry, Knowledge and Universities