Zhang Dalong, Wang Zehao, Wang Xiaojun, Yue Wenbo, Zhang Lu, Gao Zheng, Li Min, Zhou Xiaoli, Li Zhenshu, Huang Guowei, Li Wen, Zhou Dianming, Qian Zhiyong
Department of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin, China.
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.
Lipids. 2025 Jul;60(4):211-227. doi: 10.1002/lipd.12436. Epub 2025 Feb 25.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is associated with Alzheimer's disease (AD). Both docosahexaenoic acid (DHA) and medium chain triglycerides (MCTs) play essential roles in lipid metabolism and the inhibition of amyloid-β (Aβ) accumulation. We aimed to explore the possible association between cerebral Aβ deposition and the development of NAFLD and to investigate the effect of DHA combined with MCTs on delaying NAFLD progression and Aβ accumulation. To this end, 40 three-month-old APP/PS1 male mice were randomly assigned to 4 groups. The mice were fed a control diet, a DHA (2.91 g/kg) diet, an MCTs (100 g/kg) diet, or a DHA + MCTs diet for 8 months. Ten C57BL/6J mice were fed a control diet and used as the wild-type (WT) group. The results indicated that APP/PS1 mice exhibited NAFLD and cerebral Aβ accumulation. DHA combined with MCTs decreased blood and liver lipids, relieved hepatic steatosis and fat accumulation, and decreased the level of Aβ in the brain and serum. Moreover, DHA combined with MCTs significantly upregulated the levels of Aβ clearance-related proteins in the liver, modulated the expression of key hepatic lipid metabolism enzymes and upstream hepatic lipid metabolism factors. In conclusion, compared with wild-type mice, APP/PS1 mice may be more sensitive to changes in lipid metabolism due to the accumulation of Aβ. DHA combined with MCTs alleviated NAFLD and decreased brain and serum Aβ levels in APP/PS1 mice compared with the control group. The possible mechanism may involve affecting hepatic fat and cholesterol metabolism and increasing hepatic Aβ clearance by modulating liver lipid metabolism enzymes.
非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病之一，且与阿尔茨海默病（AD）相关。二十二碳六烯酸（DHA）和中链甘油三酯（MCTs）在脂质代谢及抑制淀粉样β蛋白（Aβ）积累中均发挥着重要作用。我们旨在探究脑内Aβ沉积与NAFLD发展之间的可能关联，并研究DHA联合MCTs对延缓NAFLD进展及Aβ积累的影响。为此，将40只3月龄的APP/PS1雄性小鼠随机分为4组。给这些小鼠分别喂食对照饮食、DHA（2.91 g/kg）饮食、MCTs（100 g/kg）饮食或DHA + MCTs饮食，持续8个月。10只C57BL/6J小鼠喂食对照饮食，并作为野生型（WT）组。结果表明，APP/PS1小鼠出现了NAFLD及脑内Aβ积累。DHA联合MCTs降低了血液和肝脏脂质水平，减轻了肝脏脂肪变性和脂肪积累，并降低了脑和血清中的Aβ水平。此外，DHA联合MCTs显著上调了肝脏中Aβ清除相关蛋白的水平，调节了关键肝脏脂质代谢酶及上游肝脏脂质代谢因子的表达。总之，与野生型小鼠相比，APP/PS1小鼠可能由于Aβ积累而对脂质代谢变化更为敏感。与对照组相比，DHA联合MCTs减轻了APP/PS1小鼠的NAFLD，并降低了其脑和血清中的Aβ水平。可能的机制可能涉及影响肝脏脂肪和胆固醇代谢，并通过调节肝脏脂质代谢酶增加肝脏Aβ清除。
