Liu Zhixiao, Xiao Yi, Xie Jiaying, Zhang Huiwen, Huang Qiming, Monroig Óscar, Tocher Douglas R, Liu Xiaojuan, Lin Fan, Chen Cuiying, Wang Shuqi, Li Ruixin
Guangdong Provincial Key Laboratories of Marine Biotechnology, Shantou University, Shantou 515063, China.
Institute of Aquaculture Torre de la Sal (IATS), CSIC, Ribera de Cabanes, Castellón 12595, Spain.
Aquac Nutr. 2025 Aug 30;2025:7643962. doi: 10.1155/anu/7643962. eCollection 2025.
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 (). 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.
在哺乳动物中，组织内胆固醇积累常常导致健康损害，如氧化应激。相比之下，胆固醇积累对鱼类生理健康的不利影响在很大程度上仍未得到探索。本研究调查了胆固醇积累对尼罗罗非鱼氧化应激的影响以及潜在机制。因此，将尼罗罗非鱼分别投喂对照饲料（C）或高胆固醇（1.6%，HC）饲料8周。投喂HC饲料的鱼的脏体指数（VSIs）和肝体指数（HSIs）显著升高，相应地，摄入HC导致肝脏、肠道、头肾和脾脏中胆固醇积累。摄入HC饲料影响了氧化应激，肝脏和头肾中丙二醛（MDA）水平升高以及肝脏和脾脏中过氧化氢酶（CAT）活性降低证明了这一点，而脾脏和肠道中的超氧化物歧化酶（SOD）活性增加。此外，胆固醇积累诱导肝脏和头肾中的内质网（ER）应激、炎症和凋亡，关键基因表达水平升高证明了这一点。代谢组分析表明，投喂HC饲料的罗非鱼体内代谢物水平主要富集在谷胱甘肽代谢和三羧酸循环（TCA）中，谷氨酰胺、谷氨酸、甘氨酸、柠檬酸、异柠檬酸、乌头酸、苹果酸和草酸盐水平显著降低。此外，透射电子显微镜（TEM）分析显示，投喂HC的罗非鱼肝细胞内脂滴积累以及线粒体形态明显改变。此外，在投喂HC饲料的鱼中发现血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性显著增加。总体而言，数据表明摄入HC会诱导氧化应激，这可能与抗氧化能力和线粒体功能受损有关，因为线粒体是产生细胞活性氧（ROS）的主要部位。本研究首次报道了胆固醇积累对鱼类氧化应激和健康损害的影响，并提出针对性的降胆固醇干预措施作为解决水生动物健康问题的一种有前景的治疗策略。
