Unraveling the role of salt-sensitivity genes in obesity with integrated network biology and co-expression analysis

• Published in: PloS one Vol. 15; no. 2; p. e0228400
• Main Authors: Sabir, Jamal Sabir M, El Omri, Abdelfatteh, Banaganapalli, Babajan, Aljuaid, Nada, Omar, Abdulkader M Shaikh, Altaf, Abdulmalik, Hajrah, Nahid H, Zrelli, Houda, Arfaoui, Leila, Elango, Ramu, Alharbi, Mona G, Alhebshi, Alawiah M, Jansen, Robert K, Shaik, Noor A, Khan, Muhummadh
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06-02-2020; Public Library of Science (PLoS)
• Subjects: Adipogenesis; Adipose tissue; Adiposity - drug effects; Adiposity - genetics; Adolescent; Analysis; Angiotensin; Angiotensins; Biology; Biology and Life Sciences; Biotechnology; Blood pressure; Case-Control Studies; Chronic diseases; Chronic illnesses; Computer and Information Sciences; Datasets; Development and progression; Diet; Disease; Diseases; Epistasis, Genetic - drug effects; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Gene Regulatory Networks - drug effects; Genes; Genomics; Humans; Hypertension; Identification methods; Insulin resistance; Medical research; Medicine; Medicine and Health Sciences; Metabolic disorders; Metabolic pathways; Methods; Microarray Analysis - methods; Obesity; Pathogenesis; Pediatric Obesity - genetics; Pediatric Obesity - metabolism; Pediatric Obesity - pathology; Proteins; Renin; Renin-angiotensin system; Salt; Salt Stress - drug effects; Salt Stress - genetics; Salts; Sensitivity analysis; Signal transduction; Sodium Chloride, Dietary - pharmacology; Systems Integration; Target recognition; Young Adult; Saudi Arabia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228400

Obesity is a multifactorial disease caused by complex interactions between genes and dietary factors. Salt-rich diet is related to the development and progression of several chronic diseases including obesity. However, the molecular basis of how salt sensitivity genes (SSG) contribute to adiposity in obesity patients remains unexplored. In this study, we used the microarray expression data of visceral adipose tissue samples and constructed a complex protein-interaction network of salt sensitivity genes and their co-expressed genes to trace the molecular pathways connected to obesity. The Salt Sensitivity Protein Interaction Network (SSPIN) of 2691 differentially expressed genes and their 15474 interactions has shown that adipose tissues are enriched with the expression of 23 SSGs, 16 hubs and 84 bottlenecks (p = 2.52 x 10-16) involved in diverse molecular pathways connected to adiposity. Fifteen of these 23 SSGs along with 8 other SSGs showed a co-expression with enriched obesity-related genes (r ≥ 0.8). These SSGs and their co-expression partners are involved in diverse metabolic pathways including adipogenesis, adipocytokine signaling pathway, renin-angiotensin system, etc. This study concludes that SSGs could act as molecular signatures for tracing the basis of adipogenesis among obese patients. Integrated network centered methods may accelerate the identification of new molecular targets from the complex obesity genomics data.