Natural Bioactive Compounds as Metabolic Modulators in Cultured Fish: A Critical Review of Lipid Homeostasis, Oxidative Stress, and Cellular Responses

Abstract High-fat diets (HFDs) are increasingly used in aquaculture to increase dietary energy density and spare protein for growth, but excessive lipid supply can promote hepatic lipid accumulation, oxidative stress, inflammation, intestinal dysfunction, and impaired metabolic homeostasis. Natural bioactive compounds have therefore attracted attention as functional feed additives capable of improving metabolic resilience. This critical review evaluates evidence from fish studies on curcumin, resveratrol, chlorogenic acid, berberine, quercetin, tea polyphenols, hydroxytyrosol, glycyrrhetinic acid, and related plant-derived compounds used under high-fat or high-lipid feeding conditions. Particular attention is given to mechanisms involving PPAR-mediated fatty-acid oxidation, SREBP/FAS-regulated lipogenesis, AMPK-associated energy sensing and mitochondrial quality control, Nrf2-linked antioxidant defense, and NF-κB-associated inflammatory signaling. Across the available evidence, several natural bioactives reduce hepatic or circulating lipid accumulation and improve antioxidant, inflammatory, histological, or metabolic indicators, although growth responses are less consistent. Responses depend strongly on fish species, dietary lipid level and source, bioactive dose, feeding duration, compound purity, and the physiological endpoint examined. Current evidence therefore supports selected natural bioactives primarily as metabolic modulators rather than universal growth promoters. Future research should emphasize standardized HFD models, dose-response designs, chemical characterization of extracts, correct identification of the experimental unit, mechanistic validation, and testing under commercial farming conditions. Keywords: Aquaculture, high-fat diet, phytochemicals, lipid metabolism, hepatic steatosis, oxidative stress, fish physiology