Discovery of Key Biomarkers and Novel Drug Candidates for Obesity-Associated Diabetes

Obesity and diabetes constitute a global health crisis driven by genetic factors, lifestyle influences and metabolic disruptions. Insulin resistance, [Formula: see text]-cell dysfunction, inflammation, genetic predispositions and ectopic fat accumulation underlie this complex condition, necessitating early diagnosis and strict glycemic control. Persea americana (avocado) emerges as a potential ally, with its nutrient-rich composition of monounsaturated fats, fiber, vitamins, minerals and phytochemicals that may positively influence lipid profiles, satiety, weight management and glucose metabolism. Our study employs Network Pharmacology to uncover active avocado components and targets relevant to obesity-related diabetes, utilizing methodologies like microarray analysis, survival analysis, molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. We identified 19,349 differentially expressed genes (DEGs) associated with this condition, elucidating its molecular basis. Functional annotation revealed their roles in critical biological processes (BP), cellular components (CC) and molecular functions (MF) previously implicated in therapeutic approaches. Notably, our Compound-Target-Pathway analysis highlighted key genes CYP1B1 and ESR1, influenced by avocado compounds, aligning with evidence of their involvement in metabolic regulation, inflammation and insulin sensitivity. This comprehensive perspective on avocado’s pharmacological relevance warrants further experimental validation to translate computational insights into practical diabetes management strategies.