Cholesterol Accumulation Caused Oxidative Stress Associated With Impaired Antioxidant Capability and Mitochondrial Function in the Liver of Nile Tilapia

In mammals, cholesterol accumulation in tissues often results in health damage, such as oxidative stress. In contrast, the adverse effects of cholesterol accumulation on the physiological health of fish remain largely unexplored. The present study investigated the impacts of cholesterol accumulation on oxidative stress and the potential mechanisms involved in Nile tilapia (<i>Oreochromis niloticus</i>). Thus, Nile tilapia were fed either a control diet (C) or a high-cholesterol (1.6%, HC) diet for 8 weeks. The viscero-somatic (VSIs) and hepatosomatic indices (HSIs) were increased significantly in fish fed the HC diet and, in accordance, HC intake caused the accumulation of cholesterol in the liver, intestine, head kidney, and spleen. Intake of the HC diet, affected oxidative stress as evidenced by elevated malondialdehyde (MDA) levels in the liver and head kidney and reduced catalase (CAT) activities in the liver and spleen, while SOD activities were increased in the spleen and intestine. Moreover, cholesterol accumulation induced endoplasmic reticulum (ER) stress, inflammation, and apoptosis in the liver and head kidney, as evidenced by increased expression levels of key genes. Metabolome analysis indicated that metabolite levels in tilapia fed the HC diet were primarily enriched in glutathione metabolism and the tricarboxylic acid cycle (TCA), with significantly reduced levels of glutamine, glutamate, glycine, citrate, isocitrate, aconitate, malate, and oxalate. In addition, transmission electron microscopy (TEM) analysis showed accumulation of lipid droplets and distinct alterations in the morphology of mitochondria within hepatocytes of tilapia fed HC. Moreover, significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were found in fish fed the HC diet. Overall, the data suggested that HC intake induced oxidative stress, which might be associated with impaired antioxidant capability and mitochondrial function, as mitochondria are the primary site of producing cellular reactive oxygen species (ROS). The present study is the first to report the impacts of cholesterol accumulation on oxidative stress and health damage in fish, and suggested targeted cholesterol-lowering interventions as a promising therapeutic strategy for addressing health issues in aquatic animals.