The Role of CYP1A1/2 in Cholesterol Ester Accumulation Provides a New Perspective for the Treatment of Hypercholesterolemia

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2023 Mar 6

PMID 36873188

Authors

Jian Lu

Xuyang Shang

Bingyi Yao

Dongyi Sun

Jie Liu

Yuanjin Zhang

He Wang

Jingru Shi

Huaqing Chen

Tieliu Shi

Mingyao Liu

Xin Wang

Affiliations

Soon will be listed here.

Abstract

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 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-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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