Kisspeptin and the Genetic Obesity Interactome.

Geronikolou S., Pavlopoulou A., Lambrou G., Koutelekos J., Cokkinos D., Albanopoulos K., ...More

Advances in experimental medicine and biology, vol.1339, pp.111-117, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1339
  • Publication Date: 2021
  • Doi Number: 10.1007/978-3-030-78787-5_15
  • Journal Name: Advances in experimental medicine and biology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Page Numbers: pp.111-117
  • Keywords: Genetic obesity, Homeostasis, Stress, Kisspeptin, Interactome, Systems biology, Kisspeptin signal transduction pathway, MUTATIONS, SIM1, PHENOTYPES, VARIANTS
  • Dokuz Eylül University Affiliated: Yes

Abstract

Background: Kisspeptin (encoded by the KISS1 gene in humans) is an excitatory neuromodulatory peptide implicated in multiple homeostatic systems, including anti--oxidation, glucose homeostasis, nutrition, locomotion, etc. Therefore, in the current obesity epidemic, kisspeptin is gaining increasing interest as a research objective. Aim: To construct an updated interactome of genetic obesity, including the kisspeptin signal transduction pathway. Methods: Kisspeptin and obesity-related genes or gene products were extracted from the biomedical literature, and a network of functional associations was created. Results: The generated network contains 101 nodes corresponding to gene/gene products with known and/or predicted interactions. In this interactome, KISS1 and KISS1R are connected directly to the luteinizing hormone receptor (LHCGR), gonadotropin-releasing hormone receptor (GNRH1), and indirectly, through the latter, to proopiomelanocortin (POMC), glucagon, leptin (LEP), and/or pro-protein convertase subtilisin/kexin-type 1 (PCSK1), all of which are critically implicated in obesity disorders. Conclusions: Our updated obesidome includes kisspeptin and its connections to the genetic obesity signalosome with 12 major hubs: glucagon (GCG), insulin (INS), arginine vasopressin (AVP), G protein subunit beta 1 (GNB1) and proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), leptin (LEP), gonadotropin-releasing hormone 1 (GNRH1), adrenoceptor beta 2 and 3 (ADRB2-3), glucagon-like peptide 1 receptor (GLP1R), and melanocortin 3 receptor (MC3R) genes were identified as major "hubs" for genetic obesity, providing novel insight into the body's energy homeostasis.