Leptin Signaling and Its Relationship with Obesity-induced Insulin Resistance: A Bioinformatics-assisted Review

Abstract

Obesity has become a global epidemic affecting diverse populations and leading to metabolic syndrome across different sexes and age groups. A significant aspect of obesity is the development of leptin resistance, primarily due to the inefficient transport of leptin across the blood-brain barrier and other mechanisms such as protein folding and dysregulation of leptin signaling in brain areas related to energy and adipose tissue metabolism. This hindrance in leptin delivery poses a challenge to using this adipokine as a potential therapy for obesity. Current research focuses on understanding the complex molecular pathways that link diet-induced obesity, characterized by increased levels of leptin, to the onset of metabolic syndrome. This syndrome encompasses various health issues, including type 2 diabetes mellitus, and involves intricate mechanisms primarily affecting pancreatic β-cells. This bioinformatics-assisted review describes key biological elements of known pathways, such as the forkhead box protein O1/leptin receptor and Janus kinase/signal transducer and activator of transcription 3, and discusses future directions that might contribute to understanding the relationship between obesity, leptin resistance, and metabolic complications (e.g., Rac1/cell division control protein 42 homolog), paving the way for future research on targeted therapeutic interventions.