Evidence map›Paper›PMID 36646756›Full record

ArticleNature metabolism2023

Hepatic nonvesicular cholesterol transport is critical for systemic lipid homeostasis.

Xu Xiao, John Paul Kennelly, Alessandra Ferrari, Bethan L Clifford, Emily Whang, Yajing Gao, Kevin Qian, Jaspreet Sandhu, Kelsey E Jarrett, Madelaine C Brearley-Sholto and 10 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 59 citations in OpenAlex.

  1. Design and structural basis of selective nonsteroidal inhibitors of aster cholesterol trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  13. The multimodal transcriptional response of denervated skeletal muscle involves regulation ofProceedings of the National Academy of Sciences of the United States of America · 2025
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  14. Article
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  17. PPARα regulates ER-lipid droplet protein Calsyntenin-3β to promote ketogenesis in hepatocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 1 institution in 1 country.

Xu Xiao *Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-5033-7627
John Paul Kennelly *Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-4399-3976
Alessandra FerrariDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Bethan L CliffordDepartment of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.
Emily WhangPediatric Gastroenterology, Hepatology and Nutrition, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Yajing GaoDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Kevin QianDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jaspreet SandhuDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Kelsey E JarrettDepartment of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.
Madelaine C Brearley-SholtoDepartment of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.
Alexander NguyenDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Rohith T NagariDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Min Sub LeeDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Sicheng ZhangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Thomas A WestonDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Stephen G YoungDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Steven J BensingerDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-9657-4206
Claudio J VillanuevaDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Thomas Q de Aguiar VallimDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.
Peter TontonozDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA. ptontonoz@mednet.ucla.edu.ORCID 0000-0003-1259-0477
University of California, Los Angeles · US

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
The Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3M
Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FONG, LOREN GI · 2019 to 2023
$11.7M
GASTROENTEROLOGYT32DK007180 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JENSEN, DENNIS MICHAEL · 1986 to 2025
$10.0M
The Nuclear Receptor-Aster Pathway in Enterohepatic MetabolismR01DK126779 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2020 to 2024
$2.4M
NHLBI NIH HHS P01 HL090553NHLBI NIH HHS P01 HL146358NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK126779NIDDK NIH HHS T32 DK007180NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

In cell models, changes in the 'accessible' pool of plasma membrane (PM) cholesterol are linked with the regulation of endoplasmic reticulum sterol synthesis and metabolism by the Aster family of nonvesicular transporters; however, the relevance of such nonvesicular transport mechanisms for lipid homeostasis in vivo has not been defined. Here we reveal two physiological contexts that generate accessible PM cholesterol and engage the Aster pathway in the liver: fasting and reverse cholesterol transport. During fasting, adipose-tissue-derived fatty acids activate hepatocyte sphingomyelinase to liberate sequestered PM cholesterol. Aster-dependent cholesterol transport during fasting facilitates cholesteryl ester formation, cholesterol movement into bile and very low-density lipoprotein production. During reverse cholesterol transport, high-density lipoprotein delivers excess cholesterol to the hepatocyte PM through scavenger receptor class B member 1. Loss of hepatic Asters impairs cholesterol movement into feces, raises plasma cholesterol levels and causes cholesterol accumulation in peripheral tissues. These results reveal fundamental mechanisms by which Aster cholesterol flux contributes to hepatic and systemic lipid homeostasis.

Indexed as

CholesterolLiverBiological TransportFatty AcidsHomeostasisCholesterolFatty Acids

Identifiers

PMID36646756
PMCPMC9995220
OpenAlexW4316507314

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.