美國加州大學(xué)Peter Tontonoz團(tuán)隊(duì)近期取得重要工作進(jìn)展，他們研究發(fā)現(xiàn)， Aster依賴性非囊泡型轉(zhuǎn)運(yùn)能促進(jìn)膳食膽固醇攝取。相關(guān)研究成果2023年11月10日在線發(fā)表于《科學(xué)》雜志上。
據(jù)介紹，腸道吸收是維持系統(tǒng)膽固醇穩(wěn)態(tài)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(fā)現(xiàn)Aster-B和Aster-C對腸細(xì)胞中的非囊泡型膽固醇轉(zhuǎn)運(yùn)至關(guān)重要。NPC1L1的缺失減少了可接近的質(zhì)膜（PM）膽固醇，并消除了Aster向腸道邊界的募集。缺乏Asters的腸細(xì)胞積累PM膽固醇，并顯示內(nèi)質(zhì)網(wǎng)膽固醇耗竭。Aster缺乏的小鼠膽固醇吸收受損，可以預(yù)防飲食誘導(dǎo)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(fā)現(xiàn)將Aster通路確定為膳食脂質(zhì)吸收中一個(gè)生理上重要，且藥理學(xué)上易于處理的節(jié)點(diǎn)。
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(xué)》，創(chuàng)刊于1880年。隸屬于美國科學(xué)促進(jìn)會，最新IF：63.714
官方網(wǎng)址：https://www.sciencemag.org/
投稿鏈接：https://cts.sciencemag.org/scc/
17312606166