Salidroside Promotes Fatty Acid β-Oxidation and Reduces Hepatic Lipid Deposition in Largemouth Bass by Activating Autophagy via the AMPK/mTOR Pathway

Replacing expensive fishmeal with economically viable plant-derived carbohydrates in aquafeeds holds significant promise. However, excess dietary carbohydrates can induce hepatosteatosis in fish. This study investigated the effects of salidroside (Sal) supplementation of high-carbohydrate (HC) diets on the growth, hepatic fatty acid oxidation, and lipid metabolism of largemouth bass, <i>Micropterus salmoides</i>. Sal did not enhance growth performance but significantly ameliorated morphological indices in HC-fed fish and markedly reduced hepatic triglycerides (TGs), enhanced lipolysis, and stimulated β-oxidation of fatty acids. Furthermore, Sal significantly upregulated AMPKα phosphorylation while downregulating mTOR phosphorylation, thereby activating autophagy-related gene expression. Pearson correlation analysis indicated a strong association between reduced lipid deposition and the AMPK/mTOR-mediated activation of autophagy. <i>In vitro</i> experiments confirmed that Sal activates autophagy via the AMPK/mTOR pathway, thereby mitigating the high-glucose-induced accumulation of TGs. Thus, Sal alleviates hepatic lipid deposition in largemouth bass by activating the AMPK/mTOR signaling pathway, inducing autophagy, and promoting β-oxidation of fatty acids. This study provides evidence for Sal's therapeutic potential against piscine fatty liver disease and identifies novel targets for managing pathological lipid deposition in aquaculture species.