美國加州大學Peter Tontonoz團隊近期取得重要工作進展，他們研究發現， Aster依賴性非囊泡型轉運能促進膳食膽固醇攝取。相關研究成果2023年11月10日在線發表于《科學》雜志上。
據介紹，腸道吸收是維持系統膽固醇穩態的重要因素。Niemann-Pick C1 Like 1（NPC1L1）有助于膳食膽固醇攝取的初始步驟，但膽固醇如何在NPC1L1下游移動尚不清楚。
研究人員發現Aster-B和Aster-C對腸細胞中的非囊泡型膽固醇轉運至關重要。NPC1L1的缺失減少了可接近的質膜（PM）膽固醇，并消除了Aster向腸道邊界的募集。缺乏Asters的腸細胞積累PM膽固醇，并顯示內質網膽固醇耗竭。Aster缺乏的小鼠膽固醇吸收受損，可以預防飲食誘導的高膽固醇血癥。最后，Aster通路可以用小分子抑制劑靶向，以控制膽固醇的攝取。
總之，這些發現將Aster通路確定為膳食脂質吸收中一個生理上重要，且藥理學上易于處理的節點。
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：《科學》，創刊于1880年。隸屬于美國科學促進會，最新IF：63.714
官方網址：https://www.sciencemag.org/
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