Inflammation modulates central regulation of homeostasis in rainbow trout

The expansion of aquaculture has led to increased use of high-fat diets to improve growth and reduce production costs; however, in mammals, excessive dietary fat induces hypothalamic inflammation that disrupts central regulation of food intake and energy homeostasis. In fish, while peripheral inflammatory responses to high-fat diets are documented, central inflammation and its impact on feeding regulation remain largely unexplored. In this study, we investigated how dietary lipid content and fatty acid composition influence central inflammatory signaling and neuroendocrine control of feeding and metabolism in rainbow trout (Oncorhynchus mykiss), a teleost species with well-characterized appetite regulation and high aquaculture relevance. Trout were fed diets differing in total fat and vegetable oil composition, and brain expression of inflammatory markers, including cytokines, and NF-κB, as well as key neuropeptides controlling appetite, including npy, agrp, pomc, and cart, was measured alongside metabolic indicators. High-fat diets induced central inflammation, accompanied by altered neuropeptide expression, indicating that inflammation directly modulates central homeostatic mechanisms. The intensity of the response and its effect on neuroendocrine regulation depended on the fatty acid profile, with unsaturated lipids mitigating inflammation and preserving homeostatic balance. These findings provide novel mechanistic evidence linking diet-induced central inflammation to feeding regulation and energy balance in teleosts. Optimizing lipid quality in aquafeeds is therefore essential to promote sustainable aquaculture, enhance fish welfare, reduce production costs, and maintain efficient growth, providing actionable strategies to improve the health, sustainability, and productivity of farmed fish populations.