美国加州大学Peter Tontonoz团队近期取得重要工作进展，他们研究发现， Aster依赖性非囊泡型转运能促进膳食胆固醇摄取。相关研究成果2023年11月10日在线发表于《科学》杂志上。

据介绍，肠道吸收是维持系统胆固醇稳态的重要因素。Niemann-Pick C1 Like 1（NPC1L1）有助于膳食胆固醇摄取的初始步骤，但胆固醇如何在NPC1L1下游移动尚不清楚。

研究人员发现Aster-B和Aster-C对肠细胞中的非囊泡型胆固醇转运至关重要。NPC1L1的缺失减少了可接近的质膜（PM）胆固醇，并消除了Aster向肠道边界的募集。缺乏Asters的肠细胞积累PM胆固醇，并显示内质网胆固醇耗竭。Aster缺乏的小鼠胆固醇吸收受损，可以预防饮食诱导的高胆固醇血症。最后，Aster通路可以用小分子抑制剂靶向，以控制胆固醇的摄取。

总之，这些发现将Aster通路确定为膳食脂质吸收中一个生理上重要，且药理学上易于处理的节点。

附：英文原文

Title: Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake

Author: Alessandra Ferrari, Emily Whang, Xu Xiao, John P. Kennelly, Beatriz Romartinez-Alonso, Julia J. Mack, Thomas Weston, Kai Chen, Youngjae Kim, Marcus J. Tol, Lara Bideyan, Alexander Nguyen, Yajing Gao, Liujuan Cui, Alexander H. Bedard, Jaspreet Sandhu, Stephen D. Lee, Louise Fairall, Kevin J. Williams, Wenxin Song, Priscilla Munguia, Robert A. Russell, Martin G. Martin, Michael E. Jung, Haibo Jiang, John W. R. Schwabe, Stephen G. Young, Peter Tontonoz

Issue&Volume: 2023-11-10

Abstract: Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.

DOI: adf0966

Source: https://www.science.org/doi/10.1126/science.adf0966

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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