Non-Hereditary Obesity Type Networks and New Drug Targets: An In Silico Approach

• Published in: International journal of molecular sciences Vol. 25; no. 14; p. 7684
• Main Authors: Geronikolou, Styliani A, Pavlopoulou, Athanasia, Uça Apaydin, Merve, Albanopoulos, Konstantinos, Cokkinos, Dennis V, Chrousos, George
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-07-2024
• Subjects: B cells; Body mass index; Chronic illnesses; Circadian rhythm; drug discovery; Genes; Greece; Health aspects; Hippocrates (460?-377? BC); Hypoglycemic agents; kisspeptin; natural products; Natural resources; Neurophysiology; Obesity; Online databases; stress system/inflammation-induced obesity; stress-induced obesity; systems epidemiology; Greece; stress system/inflammation-induced obesity; natural products; stress-induced obesity; drug discovery; systems epidemiology; kisspeptin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25147684

Obesity, a chronic, preventable disease, has significant comorbidities that are associated with a great human and financial cost for society. The aim of the present work is to reconstruct the interactomes of non-hereditary obesity to highlight recent advances of its pathogenesis, and discover potential therapeutic targets. Obesity and biological-clock-related genes and/or gene products were extracted from the biomedical literature databases PubMed, GeneCards and OMIM. Their interactions were investigated using STRING v11.0 (a database of known and predicted physical and indirect associations among genes/proteins), and a high confidence interaction score of >0.7 was set. We also applied virtual screening to discover natural compounds targeting obesity- and circadian-clock-associated proteins. Two updated and comprehensive interactomes, the (a) stress- and (b) inflammation-induced obesidomes involving 85 and 93 gene/gene products of known and/or predicted interactions with an average node degree of 9.41 and 10.8, respectively, were produced. Moreover, 15 of these were common between the two non-hereditary entities, namely, ADIPOQ, ADRB2/3, CCK, CRH, CXCL8, FOS, GCG, GNRH1, IGF1, INS, LEP, MC4R, NPY and POMC, while phelligridin E, a natural product, may function as a potent FOX1-DBD interaction blocker. Molecular networks may contribute to the understanding of the integrated regulation of energy balance/obesity pathogenesis and may associate chronopharmacology schemes with natural products.