Mouse carboxylesterase 1d (Ces1d) and its human ortholog CES1 have been described to possess lipase activity and play a role in hepatic triacylglycerol (TG) metabolism and very-low density lipoprotein (VLDL) assembly. Liver is a central organ regulating cholesterol synthesis, storage, transport, and elimination. It has been proposed that Ces1d/CES1 might also catalyze cholesteryl ester (CE) hydrolysis in the liver and be responsible for the hydrolysis of high-density lipoprotein (HDL)-derived CE, thus contributing to the final step in the reverse cholesterol transport (RCT) pathway, where cholesterol is secreted from the liver into bile and feces, either directly or after conversion to water-soluble bile salts. However, the proposed function of Ces1d/CES1 as a CE hydrolase is controversial. We interrogated the role hepatic Ces1d plays in cholesterol homeostasis using liver-specific Ces1d deficient mice. We rationalized that if Ces1d is a major hepatic CE hydrolase, its absence would 1) reduce in vivo RCT flux, and 2) provoke liver CE accumulation after high cholesterol diet challenge. In this study, liver-specific Ces1d KO mice did not show any difference in the flux of in vivo HDL-to-feces RCT and did not cause additional liver CE accumulation after high-fat, high cholesterol Western-type diet (WTD) feeding, thereby challenging the importance of Ces1d as a major hepatic CE hydrolase.

中文翻译：

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羧酸酯酶 1d (Ces1d) 对肝脏中的胆固醇酯水解没有贡献。

小鼠羧酸酯酶 1d (Ces1d) 及其人类直系同源物 CES1 已被描述为具有脂肪酶活性，并在肝脏三​​酰基甘油 (TG) 代谢和极低密度脂蛋白 (VLDL) 组装中发挥作用。肝脏是调节胆固醇合成、储存、运输和消除的中枢器官。有人提出，Ces1d/CES1 还可能催化肝脏中的胆固醇酯 (CE) 水解，并负责高密度脂蛋白 (HDL) 衍生的 CE 的水解，从而有助于胆固醇逆向转运的最后一步。 RCT) 途径，其中胆固醇直接或转化为水溶性胆汁盐后从肝脏分泌到胆汁和粪便中。然而，提出的 Ces1d/CES1 作为 CE 水解酶的功能是有争议的。我们使用肝脏特异性 Ces1d 缺陷小鼠研究了肝脏 Ces1d 在胆固醇稳态中的作用。我们合理化认为，如果 Ces1d 是一种主要的肝脏 CE 水解酶，它的缺失将 1）减少体内 RCT 通量，2）在高胆固醇饮食挑战后引发肝脏 CE 积累。在这项研究中，肝脏特异性 Ces1d KO 小鼠在体内 HDL-to-feces RCT 的通量方面没有表现出任何差异，并且在高脂肪、高胆固醇西式饮食 (WTD) 喂养后没有引起额外的肝脏 CE 积累，从而挑战 Ces1d 作为主要肝脏 CE 水解酶的重要性。