Targeting the leptin-ghrelin axis for obesity management: Mechanistic insights and therapeutic approaches

Endocrine hormones ghrelin and leptin play opposing roles in regulating appetite, energy homeostasis and body weight. Dysregulation of these hormones contributes significantly to the development of obesity and associated metabolic disorders. This narrative review examines the mechanisms underlying leptin and ghrelin signaling in the central nervous system, explores the molecular causes of leptin resistance and altered ghrelin secretion, and evaluates current and novel therapeutic approaches that target these hormones to treat obesity and related comorbidities. Relevant experimental, clinical, and translational studies were reviewed to provide an overview of the molecular mechanisms, physiological interactions and therapeutic potential of the leptin-ghrelin axis. The available evidence indicates that leptin promotes satiety and energy expenditure, whereas ghrelin stimulates appetite and adipogenesis. Obesity is characterized by elevated leptin levels associated with leptin resistance and reduced ghrelin levels with altered secretion patterns. Extrinsic factors, including inflammation, psychological stress and sleep deprivation, further disrupt the leptin-ghrelin axis. Promising therapeutic approaches, including leptin sensitizers, ghrelin antagonists, and combination hormone therapies, require further clinical validation. Understanding the complex interplay between leptin and ghrelin is crucial to the advancement of hormone-based obesity therapy. Future research should focus on restoring leptin sensitivity, modulating ghrelin signaling and implementing customized, multi-hormonal therapeutic techniques for long-term metabolic health.