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The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia by Jian Lu; Xuyang Shang; Bingyi Yao; Dongyi Sun; Jie Liu; Yuanjin Zhang; He Wang; Jingru Shi; Huaqing Chen; Tieliu Shi; Mingyao Liu; Xin Wang is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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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 (LXR__α__–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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Author

Jian Lu; Xuyang Shang; Bingyi Yao; Dongyi Sun; Jie Liu; Yuanjin Zhang; He Wang; Jingru Shi; Huaqing Chen; Tieliu Shi; Mingyao Liu; Xin Wang

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)