Naringin modulates hippocampal CA3 ΔFosB expression and osteocalcin levels in fructose-induced metabolic dysfunction under chronic stress: preliminary evidence for a bone–brain connection.

Metabolic dysfunction and chronic stress can affect both skeletal and brain homeostasis. Osteocalcin (OCN), a bone-derived hormone, has emerged as a potential mediator of bone–brain communication. Naringin (NAR), a citrus-derived flavonoid with antioxidant and osteoprotective properties, may modulate these responses. We investigated whether NAR affects circulating OCN and hippocampal ΔFosB expression in male Wistar rats with fructose-induced metabolic dysfunction (FRD) exposed to chronic stress (CS). Plasma OCN was measured by immunoassay, and ΔFosB-positive cells were quantified in hippocampal subregions by immunohistochemistry. CS increased OCN levels and selectively increased ΔFosB-positive cells in CA3, but not CA1, CA2, or the dentate gyrus. NAR further increased OCN levels and enhanced ΔFosB expression in CA3 under both stressed and non-stressed conditions. The concomitant modulation of a circulating bone-derived signal and a hippocampal activity-related marker suggests that NAR may influence bone–brain communication. Given the region-specific expression of the OCN receptor GPR158 in CA3, these preliminary findings raise the possibility that OCN signaling contributes to NAR-induced hippocampal responses. Further studies are required to establish whether this association reflects a functional bone–brain pathway.