Natural Bioactive Compounds Targeting Obesity-Related Molecular Pathways: Mechanisms, Clinical Evidence, and Therapeutic Perspectives

Obesity is a major global health challenge associated with insulin resistance, hypertension, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease.Although pharmacotherapy and bariatric surgery can be effective, limitations related to cost, safety, accessibility, and long-term adherence support investigation of adjunctive strategies.This review summarizes mechanistic and clinical evidence for selected natural bioactive compounds, epigallocatechin gallate, capsaicinoids, berberine, hydroxycitric acid, curcumin, and resveratrol, and soluble dietary fibers as functional food components.These interventions have been reported to modulate pathways related to AMP-activated protein kinase signaling, thermogenesis, inflammation, de novo lipogenesis, gut microbiota, and satiety; however, the clinical relevance of several proposed mechanisms remains uncertain.Randomized trials and meta-analyses generally indicate small and heterogeneous short-term effects on body weight, often approximately 0-2 kg over 4-12 weeks, with variable changes in insulin resistance, lipid profiles, blood pressure, and other cardiometabolic markers.Interpretation is limited by short trial durations, heterogeneous populations and outcomes, and substantial variation in dose and formulation.Future studies should prioritize standardized formulations, dose-response evaluation, safety assessment, and long-term randomized controlled trials using clinically meaningful endpoints.Overall, these compounds and functional food components may have a supportive role alongside lifestyle interventions and established obesity treatments, but current evidence is insufficient to support their use as stand-alone therapies.