Objectives
Obesity is reaching epidemic levels in recent decades with a growing body of research identifying predisposing genetic components. To explore the relationship of genetic factors contributing to obesity, we undertook an analytical computer-based gene profiling approach utilizing an updated list of clinically relevant and known obesity-related genes.
Methods
We compiled an updated list of 494 genes reportedly associated with obesity and utilized the GeneAnalytics profiling software and interrogated genomic databases from GeneCards to cross-reference obesity gene-sets against tissues and cells, diseases, genetic pathways, Gene Ontology (GO)-biological processes and GO-molecular functions, phenotypes and compounds.
Results
Obesity-related fields identified by GeneAnalytics algorithms included 8 diseases, 46 pathways, 62 biological processes, 22 molecular functions, 148 phenotypes, and 286 compounds impacting adipogenesis, signal transduction by G-protein coupled receptors and lipid metabolism involving insulin-related genes (IGF1, INS, IRS1). GO-biological processes identified feeding behavior, cholesterol metabolic process, glucose and cholesterol homeostasis pathways while GO-molecular processes pertained to receptor binding affecting glucose homeostasis, body weight and circulating insulin and triglyceride levels.
Conclusions
The gene-profiling model suggests that pathogenesis of obesity relates to the coordination of biological responses to glucose and intracellular lipids possibly through a disruption of biochemical cascades and cellular signaling arising from affected receptors.