| Summary: | This study aimed to characterize the effects of resveratrol on the redox balance, cholesterol homeostasis and bile acid metabolism of <i>Megalobrama amblycephala</i> offered a high-carbohydrate diet. Fish (35.0 ± 0.15 g) were fed four diets including one control diet (32% nitrogen-free extract), one high-carbohydrate diet (45% nitrogen-free extract, HC), and the HC diet supplemented with different levels (0.04%, HCR1; 0.08%, HCR2) of resveratrol for 12 weeks. The HC diet-induced redox imbalance is characterized by increased MDA content and decreased T-SOD and CAT activities in the liver. Resveratrol attenuated this by up-regulating the transcription of <i>Cu/Zn-sod</i>, and increasing the activities of T-SOD, CAT, and GPX. The HC diet enhanced the cholesterol synthesis, but decreased the bile acid synthesis via up-regulating both <i>hmgcr</i> and <i>acat2</i>, and down-regulating <i>cyp7a1</i>, thus resulting in excessive cholesterol accumulation. Resveratrol supplement decreased cholesterol synthesis, and increased cholesterol uptake in the liver by down-regulating both <i>hmgcr</i> and <i>acat2</i>, and up-regulating <i>ldlr</i>. It also increased bile acid synthesis and biliary excretion by up-regulating <i>cyp7a1</i>, and down-regulating <i>mrp2</i>, <i>oatp1</i>, and <i>oatp4</i> in the hindgut, thereby decreasing cholesterol accumulation. In conclusion, resveratrol improves the cholesterol homeostasis of <i>Megalobrama amblycephala</i> fed a high-carbohydrate diet by modulating the redox response and bile acid metabolism.
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