Docosahexaenoic acid alleviated liver lipid deposition and health damage induced by cholesterol accumulation in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂)

Cholesterol accumulation can be a critical pathological marker and, while, the cholesterol-lowering potential of docosahexaenoic acid (DHA) has been documented extensively in mammals, its effects in fish are unclear. The present study investigated the adverse effects of cholesterol accumulation on liver health, and evaluated DHA as a potential cholesterol-lowering agent to mitigate liver damage induced by high cholesterol (HC) intake in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). Grouper were fed either a control diet or an HC (1.6 %) diet supplemented with varying levels of DHA (0, 0.5, 1, 2 %) for eight weeks. The HC diet significantly increased condition factor (CF), mesenteric fat index (MFI), and lipid, cholesterol and triglyceride accumulation in liver. Supplementing the HC diet with 0.5 % DHA significantly reduced CF, MFI and liver lipid contents. Moreover, HC intake increased aspartate transaminase (AST) and alanine transaminase (ALT) activities in serum, and malondialdehyde (MDA) content and the expression of gene related to inflammatory responses and apoptosis in liver. In addition, HC intake significantly reduced mitochondrial biogenesis and total antioxidant capacity in liver. However, supplementing the HC diet with 0.5 % DHA significantly decreased liver cholesterol accumulation by inhibiting cholesterol synthesis and promoting cholesterol efflux, and significantly reduced liver triglyceride content by inhibiting the expression of genes associated with lipogenesis and lipid droplet formation. Furthermore, supplementation of the HC diet with 0.5 % DHA significantly reduced the activities of ALT and AST in serum, and MDA content and the expression of genes associated with inflammation, apoptosis and antioxidation in liver, and enhanced liver mitochondrial biogenesis. Overall, the results indicated that DHA supplementation mitigated liver cholesterol accumulation by inhibiting cholesterol synthesis and promoting cholesterol efflux, and enhanced mitochondrial function, boosted antioxidant capacity, and reduced inflammation in liver of grouper fed the HC diet, ultimately alleviating liver damage caused by cholesterol accumulation. The present study elucidated the detrimental effects of cholesterol accumulation on liver health in aquatic animals and proposed DHA as a potential intervention for mitigating health issues associated with cholesterol overload.