CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Mar Drugs. 2021 Aug 26;19(9):485. doi: 10.3390/md19090485.
Dysregulation of cholesterol homeostasis is a major risk factor of atherosclerosis, which can lead to serious health problems, including heart attack and stroke. Liver X receptor (LXR) α and β are transcription factors belonging to the nuclear receptor superfamily, which play important roles in cholesterol homeostasis. Selectively activating LXRβ provides a promising strategy for the treatment of atherosclerosis. Here, we employed atherosclerotic apoE-knockout mice to evaluate the effects of saringosterol, a phytosterol with potent and selective action for LXRβ, which we identified previously in edible marine seaweed . We found that saringosterol treatment reduced the atherosclerotic plaque burden without having undesirable adverse hepatic effects in apoE-deficient mice fed an atherogenic diet. Meanwhile, reduced serum levels of cholesterol, accompanied by altered expression of LXR-regulated genes involved in cholesterol absorption, transport, efflux, excretion, and elimination, were observed in apoE-knockout mice after saringosterol treatment. Together, our study not only establishes saringosterol as an effective cholesterol-lowering and anti-atherogenic phytosterol but also provides insights into the underlying mechanism.
胆固醇稳态失调是动脉粥样硬化的一个主要危险因素，可导致严重的健康问题，包括心脏病发作和中风。肝 X 受体 (LXR)α和β是核受体超家族的转录因子，在胆固醇稳态中发挥重要作用。选择性激活 LXRβ为动脉粥样硬化的治疗提供了一种有前途的策略。在这里，我们使用动脉粥样硬化 apoE 基因敲除小鼠来评估 previously 在可食用海洋海藻中发现的具有强大和选择性作用的植物甾醇——菜油甾醇对动脉粥样硬化的影响。我们发现，在喂食致动脉粥样硬化饮食的 apoE 缺陷小鼠中，菜油甾醇治疗可减少动脉粥样硬化斑块负担，而不会对肝脏产生不良影响。同时，在 apoE 基因敲除小鼠中，我们观察到血清胆固醇水平降低，同时与胆固醇吸收、转运、外排、排泄和消除相关的 LXR 调节基因的表达发生改变。总之，我们的研究不仅确立了菜油甾醇作为一种有效的降胆固醇和抗动脉粥样硬化植物甾醇，还为其潜在机制提供了深入了解。
