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(LXRa-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.
基金
supported in whole or part by grants from the National Natural Science Foundation of China(81773808,82274010)
the Science and Technology Commission of Shanghai Municipality(18430760400,China)
the Jointed PI Program from Shanghai Changning Maternity and Infant Health Hospital(2019CNECNUPI02,China)
the Fundamental Research Funds for the Central Universities(China)
ECNU Construction Fund of Innovation and Entrepreneurship Laboratory(China)
supported from ECNU Multifunctional Platform for Innovation(011,China)
the Instruments Sharing Platform of School of Life Sciences,East China Normal University(Shanghai,China)。
