Chen Yishu, Zheng Kangdi, Leng Yang, Zhang Zhao, Li Xiaoling, Li Xiaoyan, Ou Huajun, Wen Muhao, Qiu Feng, Yu Huajun
Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China.
Guangdong Longseek Testing Co., Ltd., Guangzhou, China.
Front Nutr. 2025 Mar 3;12:1522982. doi: 10.3389/fnut.2025.1522982. eCollection 2025.
Hyperlipidemia is regarded as one of the crucial factors leading to atherosclerosis and other cardiovascular diseases. Gut microbiota plays an important role in regulating host lipid metabolism. Nevertheless, the exact mechanisms behind this remain unclear.
In the present study, a hyperlipidemic zebrafish model was established using a high-cholesterol diet (HCD) to evaluate the anti-hyperlipidemic effects of E15 ( E15).
Results showed that E15 effectively reduced lipid accumulation in the blood vessels and liver of HCD-fed zebrafish larvae. Meanwhile, E15 improved abnormal lipid levels, and normalized liver enzyme activity. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that E15 downregulated the expression of sterol regulatory element-binding factor (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-), and fatty acid synthase (Fasn), while upregulated peroxisome proliferator-activated receptor-alpha (PPAR-). Additionally, metabolomic analysis revealed that E15 produced a series of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid, and isovaleric acid. Notably, isovaleric acid contributed to the reduction of lipid droplet accumulation in the liver and blood vessels of HCD-fed zebrafish larvae. In contrast, blocking G-protein coupled receptor 43 (GPR43) with pertussis toxin (PTX) abolished the effects of E15 and isovaleric acid on reducing lipid accumulation in HCD-fed zebrafish larvae. RT-qPCR results further suggested that both E15 and isovaleric acid promoted the expression of GPR43 and leptin A, which was inhibited by PTX.
These findings suggested that E15 alleviates HCD-induced hyperlipidemia by activating GPR43 through SCFAs.
高脂血症被认为是导致动脉粥样硬化和其他心血管疾病的关键因素之一。肠道微生物群在调节宿主脂质代谢中发挥着重要作用。然而，其背后的确切机制仍不清楚。
在本研究中，使用高胆固醇饮食（HCD）建立高脂血症斑马鱼模型，以评估E15的抗高脂血症作用。
结果表明，E15有效减少了喂食HCD的斑马鱼幼虫血管和肝脏中的脂质积累。同时，E15改善了异常脂质水平，并使肝酶活性恢复正常。实时定量聚合酶链反应（RT-qPCR）分析显示，E15下调了固醇调节元件结合因子（SREBP-1）、过氧化物酶体增殖物激活受体γ（PPAR-γ）和脂肪酸合酶（Fasn）的表达，而上调了过氧化物酶体增殖物激活受体α（PPAR-α）的表达。此外，代谢组学分析显示，E15产生了一系列短链脂肪酸（SCFA），包括乙酸、丙酸、丁酸和异戊酸。值得注意的是，异戊酸有助于减少喂食HCD的斑马鱼幼虫肝脏和血管中的脂滴积累。相反，用百日咳毒素（PTX）阻断G蛋白偶联受体43（GPR43）消除了E15和异戊酸对减少喂食HCD的斑马鱼幼虫脂质积累的作用。RT-qPCR结果进一步表明，E15和异戊酸均促进了GPR43和瘦素A的表达，而PTX抑制了这种表达。
这些发现表明，E15通过SCFA激活GPR43来减轻HCD诱导的高脂血症。
