Obesity-driven hunger: From pathophysiology to intervention

Obesity is a complex metabolic disorder driven by an imbalance between energy intake and expenditure. A critical pathogenetic component of obesity is dysregulated hunger and satiety mechanisms, driven by both central and peripheral factors. This review explores the pathophysiology of obesity-induced hunger, focusing on key mechanisms involving neurohormonal signals, gut-brain communication, and the dysregulation of appetite-related pathways. It discusses the roles of hormones such as ghrelin, leptin, and insulin, as well as the influence of inflammatory processes on hunger regulation. Additionally, environmental and psychological factors contributing to food cravings and reward-driven eating are considered. The article also examines current and emerging therapeutic interventions targeting hunger and appetite control, including pharmacologic treatments, such as glucagon-like peptide-1 (GLP-1) receptor agonists, lifestyle modifications, and bariatric surgery. Novel strategies under investigation, including appetite-regulating peptides, are highlighted. Bridging the understanding of the intricate mechanisms driving obesity-related hunger with therapeutic advances provides a comprehensive framework for more effective treatment strategies to combat obesity and its associated comorbidities which will ultimately improve patient outcomes. • Obesity involves dysregulated hunger and satiety via central, peripheral, and neurohormonal mechanisms. • Key hormones like ghrelin, leptin, and insulin significantly impact appetite regulation and hunger. • Environmental and psychological factors drive food cravings and reward-based eating behaviors. • Emerging therapies, including GLP-1 agonists, peptides, and surgery, target hunger and appetite control.