RT Journal Article T1 Immunoneuroendocrine, Stress, Metabolic, and Behavioural Responses in High-Fat Diet-Induced Obesity A1 Navarro, María del Carmen A1 Gálvez, Isabel A1 Hinchado, Isabel A1 Otero, Eduardo A1 Torres Piles, Silvia A1 Francisco Morcillo, Javier A1 Fuente Del Rey, María Mónica De La A1 Martín Cordero, Leticia A1 Ortega, Eduardo AB Obesity has reached global epidemic proportions, and even though its effects are well-documented, studying the interactions among all influencing factors is crucial for a better understanding of its physiopathology. In a high-fat-diet-induced obesity animal model using C57BL/6J mice, behavioural responses were assessed through a battery of tests, while stress biomarkers and systemic inflammatory cytokines were measured using an Enzyme-Linked ImmunoSorbent Assay and a Bio-Plex Multiplex System. The peritoneal macrophage microbicide capacity was analysed via flow cytometry, and crown-like structures (CLSs) in white adipose tissue (WAT) were evaluated through staining techniques. Results indicated that obese mice exhibited increased body weight, hyperglycaemia, and hyperlipidaemia after 18 weeks on a high-fat diet, as well as worse physical conditions, poorer coordination and balance, and anxiety-like behaviour. Differences in corticosterone and noradrenaline concentrations were also found in obese animals, revealing a stress response and noradrenergic dysregulation, along with a weakened innate immune response characterized by a lower microbicide capacity, and the presence of an underlying inflammation evidenced by more CLSs in WAT. Altogether, these findings indicate that obesity deteriorates the entire stress, inflammatory, metabolic, sensorimotor and anxiety-like behavioural axis. This demonstrates that jointly evaluating all these aspects allows for a deeper and better exploration of this disease and its associated comorbidities, emphasizing the need for individualized and context-specific strategies for its management. PB MDPI SN 2072-6643 YR 2024 FD 2024 LK https://hdl.handle.net/20.500.14352/118012 UL https://hdl.handle.net/20.500.14352/118012 LA eng NO Navarro, M.d.C.; Gálvez, I.; Hinchado, M.D.; Otero, E.; Torres-Piles, S.; Francisco-Morcillo, J.; de La Fuente, M.; Martín-Cordero, L.; Ortega, E. Immunoneuroendocrine, Stress, Metabolic, and Behavioural Responses in High-Fat Diet-Induced Obesity. Nutrients 2024, 16, 2209. https://doi.org/10.3390/nu16142209 NO This research was funded by the Gobierno de Extremadura-Fondo Europeo de Desarrollo Regional, Spain (GR21079; IB18011). NO Gobierno de Extremadura NO European Commission DS Docta Complutense RD 21 abr 2025