Gut‐Brain‐Adipose Tissue Crosstalk in Incretin‐Based Obesity Therapeutics: Molecular Networks Driving Metabolic Homeostasis and Disease

ABSTRACT Obesity is a complex systems‐level disorder characterized by disrupted interorgan communication across the gut‐brain‐adipose‐liver axis. This study examines how hepatic lipid metabolism, adipose tissue remodeling, and central satiety pathways are modulated by incretin hormones (GLP‐1 and GIP), which function as master regulators of energy balance. Importantly, we emphasize how host genetics, oxysterol‐driven signaling pathways, and metabolites generated from the microbiome, like short‐chain fatty acids, interact to shape treatment responsiveness. The shift from organ‐specific management to next‐generation precision obesity therapies is made easier by incorporating these multi‐omics networks into a pharmacomicrobiomics framework, which maximizes clinical efficacy and reduces interindividual treatment variability.