Understanding how vertebrate brains evolved to control hunger could unlock more effective treatments for obesity and eating disorders affecting millions worldwide. The fundamental neural machinery governing appetite appears far more ancient and conserved than previously recognized. A*STAR researchers mapped hypothalamic appetite networks in both zebrafish and mice, discovering that core hunger-regulating circuits have remained virtually unchanged across 400 million years of vertebrate evolution. The team identified specific neuronal populations and molecular pathways that control feeding behavior identically in both species, despite their vast evolutionary separation. Key neurotransmitter systems and their connectivity patterns showed remarkable preservation, suggesting these circuits represent essential biological architecture that natural selection has maintained across vertebrate lineages. This conservation extends to the cellular level, with similar gene expression profiles and synaptic organizations governing appetite control in both organisms. The findings represent a significant advance in comparative neuroscience, demonstrating that appetite regulation involves deeply embedded evolutionary programming rather than species-specific adaptations. For human health applications, this research validates zebrafish as highly relevant models for studying obesity, anorexia, and metabolic disorders. The evolutionary conservation suggests that therapeutic targets identified in simpler model organisms will likely translate effectively to human treatments. This discovery also implies that appetite dysregulation represents disruption of ancient, fundamental biological processes rather than modern lifestyle-induced phenomena. The research provides a strong foundation for developing precision therapies that work with, rather than against, these deeply conserved neural mechanisms that have successfully regulated feeding across vertebrate species for hundreds of millions of years.