Evidence map›Paper›PMID 30242108›Full record

ArticleJournal of lipid research2018

NPC1L1-dependent intestinal cholesterol absorption requires ganglioside GM3 in membrane microdomains.

Wataru Nihei, Masakazu Nagafuku, Hirotaka Hayamizu, Yuta Odagiri, Yumi Tamura, Yui Kikuchi, Lucas Veillon, Hirotaka Kanoh, Kei-Ichiro Inamori, Kenta Arai and 3 more

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

Article in Journal of lipid research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

11 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Ganglioside GM3 Synthase Deficiency in Mouse Models and Human Patients.International journal of molecular sciences · 2022
    Review
  8. Ezetimibe and Cancer: Is There a Connection?Frontiers in pharmacology · 2022
    Review
  9. Mechanisms and regulation of cholesterol homeostasis.Nature reviews. Molecular cell biology · 2020
    Review
  10. Review
  11. Glycosphingolipids and Infection. Potential New Therapeutic Avenues.Frontiers in cell and developmental biology · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Wataru NiheiDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Masakazu NagafukuDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Hirotaka HayamizuDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Yuta OdagiriDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Yumi TamuraDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Yui KikuchiDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Lucas VeillonDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Hirotaka KanohDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Kei-Ichiro InamoriDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Kenta AraiLaboratory of Natural Product Chemistry, Department of Chemistry, Osaka University, Toyonaka, Japan.
Kazuya KabayamaLaboratory of Natural Product Chemistry, Department of Chemistry, Osaka University, Toyonaka, Japan.
Koichi FukaseLaboratory of Natural Product Chemistry, Department of Chemistry, Osaka University, Toyonaka, Japan.
Jin-Ichi InokuchiDivision of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan jin@tohoku-mpu.ac.jp.
Tohoku Medical and Pharmaceutical University · JPOsaka University · JPThe University of Texas MD Anderson Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intestinal cholesterol absorption is a key regulator of systemic cholesterol homeostasis. Excessive dietary cholesterol and its intestinal uptake lead to hypercholesterolemia, a major risk factor for cardiovascular disease. Intestinal cholesterol uptake is mediated by Niemann-Pick C1-like 1 (NPC1L1), a transmembrane protein localized in membrane microdomains (lipid rafts) enriched in gangliosides and cholesterol. The roles of gangliosides, such as monosialodihexosylganglioside (GM3) and its synthesizing enzyme GM3 synthase (GM3S), in NPC1L1-dependent cholesterol uptake have not been examined previously. Here, we examined NPC1L1-dependent cholesterol uptake in a cell model as well as in wild-type and apoE-deficient mice fed normal or high-cholesterol diets. We showed that NPC1L1-dependent cholesterol uptake was impaired in GM3S-deficient cells and that GM3S deficiency promoted resistance to hypercholesterolemia in both wild-type and apoE-deficient mice fed the high-cholesterol but not the normal diet. Our findings suggest that GM3 and related gangliosides are essential for NPC1L1-mediated intestinal cholesterol absorption and are potential targets for hypercholesterolemia therapy.

Indexed as

AnimalsBiological TransportCholesterolG(M3) GangliosideHEK293 CellsHumansHypercholesterolemiaImmunohistochemistryIntestinal AbsorptionLipoproteinsMaleMembrane MicrodomainsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, KnockoutCholesterolG(M3) GangliosideLipoproteinsMembrane Transport ProteinsNpc1l1 protein, mousecholesterol absorptiongangliosideshypercholesterolemialipid transportmonosialodihexosylgangliosideNiemann-Pick C1-like 1

Identifiers

PMID30242108
PMCPMC6210914
OpenAlexW2891907398

What OpenQuestion holds

Textmetadata
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.