The correlation between obesity and leptin signaling pathways

Abstract

Obesity is a global epidemic associated with increased morbidity and mortality. It is a major risk factor for the development of chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and certain cancers, primarily due to excessive fat accumulation in the body. Both environmental and genetic factors contribute to the development of obesity. A key pathophysiological feature of obesity is resistance to the metabolic hormones leptin and ghrelin, which play critical roles in neuroendocrine regulation of energy homeostasis. Leptin, a proinflammatory peptide hormone encoded by the obese (ob) gene, is primarily secreted by white adipose tissue. It functions as an anti-obesity hormone by suppressing appetite, reducing food intake, and increasing energy expenditure. Leptin resistance, resulting from altered expression of leptin (LEP) and its receptor (LEP-R), impairs its regulatory effects on energy balance. Additionally, aberrant leptin signaling and genetic mutations in the leptin gene or its receptor are associated with morbid obesity and other related diseases. The treatment of obesity using leptin-based therapeutics may be one of the methods to treat obesity. The present review aimed to explore the molecular mechanisms of leptin signaling, leptin resistance in obesity, and the potential of leptin-based therapies as novel interventions in obesity management.

Keywords: Energy homeostasis; Genetic mutation; Leptin; Obesity.