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. 2021:1339:111-117.
doi: 10.1007/978-3-030-78787-5_15.

Kisspeptin and the Genetic Obesity Interactome

Geronikolou S  1 , Athanassia Pavlopoulou  2 , George I Lambrou  3 , John Koutelekos  4 , Dennis Cokkinos  5 , Konstantinos Albanopoulos  6 , George P Chrousos  7
Affiliations

Kisspeptin and the Genetic Obesity Interactome

Geronikolou S et al. Adv Exp Med Biol. 2021.

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.

Keywords: Genetic obesity; Homeostasis; Interactome; Kisspeptin; Kisspeptin signal transduction pathway; Stress; Systems biology.

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References

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