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CYP4A14-PPARα轴作为ursodeoxycholic酸的治疗点,可以改善高脂肪饮食引起的MASLD

Bing Li¹, Pengjun Zhong¹, Xueling Zhang¹

¹School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, PR China.

The Journal of nutritional biochemistry

|October 8, 2025

概括

乌尔索多胆酸 (UDCA) 通过激活PPARα-CYP4A14通路,减少肝脂肪和炎症,有效治疗与代谢功能障碍相关的脂肪性肝病 (MASLD). 这项研究揭示了UDCA的新型机制.

科学领域:

肝病学肝病学是一种肝病学.
代谢疾病代谢疾病
药理学药理学是指药理学的学科.

背景情况:

与代谢功能障碍相关的脂肪性肝病 (MASLD) 是一个日益严重的全球健康问题,没有批准的治疗方法.
一种胆汁酸的乌尔索多西胆酸 (UDCA) 对MASLD治疗具有前景,但其机制尚不清楚.

研究的目的:

为了阐明UDCA在MASLD中的精确肝脏保护机制.
为了研究UDCA对肝硬化,炎症和代谢障碍的影响.

主要方法:

高脂肪饮食 (HFD) 诱导的MASLD小鼠模型.
在体外研究中使用AML12肝细胞挑战脂肪酸 (PA/OA).
PPARα和CYP4A14通路分析,包括siRNA淘汰和分子模拟.

主要成果:

在小鼠中,UDCA缓解了HFD诱导的肝肥胖症,炎症和代谢问题.
UDCA激活了肝脏PPARα和CYP4A14,增强了β脂肪酸的氧化.
在实验室中,UDCA降低了脂质积累和肝酶释放,PPARα-CYP4A14倒置减轻了这些影响.

结论:

UDCA通过一种新的PPARα-CYP4A14信号通路发挥抗MASLD作用.
UDCA可能直接调节CYP4A14,为MASLD提供治疗点.
这项研究为考虑UDCA作为潜在的MASLD治疗剂提供了基础.

关键词:

在CYP4A14中.脂质代谢脂质代谢是一种马斯尔德马斯尔德是什么意思这是一种PPARα.Ursodeoxycholic 酸是一种抗氧化的药物 .

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