ESPE Abstracts

Background: Kisspeptin (encoded by the KISS1 gene in humans), originally described as a puberty onset regulating neuropeptide, is involved in many homeostatic systems, including nutrition status, glucose homeostasis, locomotor activity, etc. Thus, in today’s obesity epidemic, kisspeptin is gaining increasing interest as a research target.

Aim: To construct an updated interactome of genetic determinants of obesity, including the kisspeptin signal transduction pathway.

Methods: Kisspeptin and obesity-related genes or gene products were extracted from the biomedical literature (Geronikolou 2017, Styne, 2017, Nead 2015, Huyene 2015, Schaaf 2013, Ckallis 2013, Mead 2007, Krude 1998). The interactions among the obesity-related genes or gene products, were generated and visualized by employing STRING v10 (Szklarczyk et al., 2015), with a high confidence interaction score of 0.7-0.97.

Results: The intermediate nodes predicted that KISS1 and KISS1 receptor are connected directly to the luteinizing hormone receptor (LHR), the gonadotropin-releasing hormone receptor (GNHR) and, indirectly, through them to propiomelanocortin, glucagon, leptin and/or proprotein convertase subtilisin/kexin-type- 1. This interactome contains 46 nodes of gene- gene products of known and/or predicted interactions.

Conclusions: Our proposed updated obesidome includes kisspeptin and its connections to the genetic determinants of obesity. The gonadotropin-releasing hormone receptor, glucagon and pro-opiomelanocortin genes were identified as major “hubs” of the the obesidome, providing novel insights into body’s energy homeostasis and an explanation for the earlier onset of puberty in obese girls.