Evidence map›Paper›PMID 26114596›Full record

ArticleeLife2015

Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways.

Matthew A Mitsche, Jeffrey G McDonald, Helen H Hobbs, Jonathan C Cohen

Abstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

120 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Effect of epigenetics on vitamin D levels: a systematic review until December 2020.Archives of public health = Archives belges de sante publique · 2023
    Pooled it
  2. Serum 4β-hydroxycholesterol increases during fluconazole treatment.European journal of clinical pharmacology · 2021
    Trial
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60 more citing papers are in PubMed but not listed here.

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

4 authors.

Matthew A MitscheDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.
Jeffrey G McDonaldDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.
Helen H HobbsDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.
Jonathan C CohenCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, United States.

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI RUSSELL, DAVID W. · 1985 to 2021
$103.1M
UT Southwestern Center for Translational Medicine (UL1/KL2/TL1)UL1TR001105 · NCATS · UT SOUTHWESTERN MEDICAL CENTER · PI TOTO, ROBERT DANIEL · 2013 to 2017
$24.5M
Role of ABCG5 and ABCG8 in Sterol MetabolismR37HL072304 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HOBBS, HELEN HASKELL · 2008 to 2017
$4.5M
Determining the Function of PNPLA3 Utilizing Metabolomics and Stable Isotope LabeK01GM109317 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI MITSCHE, MATTHEW ALVIN · 2013 to 2016
$413k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001105NCATS NIH HHS UL1TR001105NHLBI NIH HHS P01 HL020948NHLBI NIH HHS P01 HL20948NHLBI NIH HHS R37HL72304NIGMS NIH HHS K01 GM109317NIGMS NIH HHS K01GM109317
6 · The paper itself

Abstract

Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling and isotopomer analysis to trace sterol flux through the two pathways in mice. Surprisingly, no tissue used the canonical K-R pathway. Rather, a hybrid pathway was identified that we call the modified K-R (MK-R) pathway. Proportional flux through the Bloch pathway varied from 8% in preputial gland to 97% in testes, and the tissue-specificity observed in vivo was retained in cultured cells. The distribution of sterol isotopomers in plasma mirrored that of liver. Sterol depletion in cultured cells increased flux through the Bloch pathway, whereas overexpression of 24-dehydrocholesterol reductase (DHCR24) enhanced usage of the MK-R pathway. Thus, relative use of the Bloch and MK-R pathways is highly variable, tissue-specific, flux dependent, and epigenetically fixed. Maintenance of two interdigitated pathways permits production of diverse bioactive sterols that can be regulated independently of cholesterol.

Indexed as

Metabolic Flux AnalysisAnimalsAnimal StructuresCells, CulturedCholesterolIsotope LabelingMicePlasmaCholesterolbiochemistrycholesterol metabolismdeuteriumisotopomermass spectrometrymousestable isotope

Identifiers

PMID26114596
PMCPMC4501332

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.