胆固醇
肝X受体
胆固醇逆向转运
化学
平衡
内科学
内分泌学
甾醇调节元件结合蛋白
脂肪生成
高密度脂蛋白
脂蛋白
甾醇
生物化学
生物
医学
转录因子
脂质代谢
核受体
基因
作者
Jian Lu,Xuyang Shang,Bingyi Yao,Dongyi Sun,Jie Liu,Yuanjin Zhang,David Simchi-Levi,Jingru Shi,Huaqing Chen,Tieliu Shi,Mingyao Liu,Xin Wang
标识
DOI:10.1016/j.apsb.2022.08.005
摘要
Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
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