Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake-Reference-Cited by-同舟云学术

Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake

Published:2023-11-10 Issue:6671 Volume:382 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Ferrari Alessandra¹²^ORCID,Whang Emily¹²³^ORCID,Xiao Xu¹²^ORCID,Kennelly John P.¹²^ORCID,Romartinez-Alonso Beatriz⁴^ORCID,Mack Julia J.⁵^ORCID,Weston Thomas⁵⁶^ORCID,Chen Kai⁷⁸^ORCID,Kim Youngjae⁹^ORCID,Tol Marcus J.¹²,Bideyan Lara¹²^ORCID,Nguyen Alexander¹²¹⁰^ORCID,Gao Yajing¹²^ORCID,Cui Liujuan¹²^ORCID,Bedard Alexander H.¹²^ORCID,Sandhu Jaspreet¹¹¹,Lee Stephen D.¹²^ORCID,Fairall Louise⁴^ORCID,Williams Kevin J.²¹²^ORCID,Song Wenxin⁵⁶^ORCID,Munguia Priscilla⁵⁶,Russell Robert A.¹³^ORCID,Martin Martin G.³^ORCID,Jung Michael E.⁹^ORCID,Jiang Haibo⁷⁸^ORCID,Schwabe John W. R.⁴^ORCID,Young Stephen G.⁵⁶^ORCID,Tontonoz Peter¹²^ORCID

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

2. Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

3. Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

4. Institute for Structural and Chemical Biology, University of Leicester, Leicester LE1 7RH, UK.

5. Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

6. Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

7. Department of Chemistry, The University of Hong Kong, Hong Kong 999077, China.

8. School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia.

9. Department of Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

10. Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine

11. Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

12. UCLA Lipidomics Core, University of California, Los Angeles, Los Angeles, CA 90095, USA.

13. National Deuteration Facility, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

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

Reference65 articles.

1. Genetic demonstration of intestinal NPC1L1 as a major determinant of hepatic cholesterol and blood atherogenic lipoprotein levels

2. The Biogenesis of Chylomicrons

3. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice

4. Cholesterol esterification by ACAT2 is essential for efficient intestinal cholesterol absorption: evidence from thoracic lymph duct cannulation

5. Tissue-specific knockouts of ACAT2 reveal that intestinal depletion is sufficient to prevent diet-induced cholesterol accumulation in the liver and blood

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