Evidence map›Paper›PMID 33785425›Full record

ArticleMolecular metabolism2021

Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice.

Rachel M B Bell, Elisa Villalobos, Mark Nixon, Allende Miguelez-Crespo, Lee Murphy, Angie Fawkes, Audrey Coutts, Matthew G F Sharp, Martha V Koerner, Emma Allan and 9 more

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Article
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  6. Article
  7. Sanger Sequencing Reveals Novel Variants inMedicina (Kaunas, Lithuania) · 2024
    Article
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  9. Article
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

19 authors at 7 institutions in 4 countries.

Rachel M B BellBritish Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: rachel.bell@ed.ac.uk.
Elisa VillalobosBritish Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: evillalo@exseed.ed.ac.uk.
Mark NixonBritish Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: m.nixon@ed.ac.uk.
Allende Miguelez-CrespoBritish Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: amiguele@exseed.ed.ac.uk.
Lee MurphyGenetics Core, Edinburgh Clinical Research Facility, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: lee.murphy@ed.ac.uk.
Angie FawkesGenetics Core, Edinburgh Clinical Research Facility, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: a.fawkes@ed.ac.uk.
Audrey CouttsGenetics Core, Edinburgh Clinical Research Facility, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: aduncan5@exceed.ed.ac.uk.
Matthew G F SharpTransgenics Core, Bioresearch & Veterinary Services, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: matthew.sharp@ed.ac.uk.
Martha V KoernerTransgenics Core, Bioresearch & Veterinary Services, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: m.koerner@ed.ac.uk.
Emma AllanTransgenics Core, Bioresearch & Veterinary Services, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: emma.murdoch@igmm.ed.ac.uk.
Onno C MeijerDepartment of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: o.c.meijer@lumc.nl.
Renè HoutmanPamgene International, Den Bosch, the Netherlands. Electronic address: rene@precisionmedicinelab.nl.
Alex OdermattDivision of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. Electronic address: alex.odermatt@unibas.ch.
Katharina R BeckDivision of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. Electronic address: katharina.beck@wlab.gu.se.
Scott G DenhamMass Spectrometry Core Laboratory, Wellcome Trust Clinical Research Facility, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: scott.denham@ed.ac.uk.
Patricia LeeMass Spectrometry Core Laboratory, Wellcome Trust Clinical Research Facility, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: t.lee1@exceed.ed.ac.uk.
Natalie Z M HomerMass Spectrometry Core Laboratory, Wellcome Trust Clinical Research Facility, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: n.z.m.homer@ed.ac.uk.
Brian R WalkerBritish Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address: brian.walker@newcastle.ac.uk.
Ruth A MorganBritish Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom. Electronic address: ruth.morgan@ed.ac.uk.
British Heart Foundation · GBThe Queen's Medical Research Institute · GBUniversity of Edinburgh · GBWestern General Hospital · GBUniversity of Basel · CHLeiden University Medical Center · NLRobert Bosch (Germany) · DE

Funding

Wellcome TrustWellcome Trust 206587/Z/17/Z
6 · The paper itself

Abstract

objectiveCarbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone to 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose tissue of obese humans and mice and may contribute to cardiometabolic complications of obesity. This study tested the hypothesis that Cbr1-mediated glucocorticoid metabolism influences glucocorticoid and mineralocorticoid receptor activation in adipose tissue and impacts glucose homeostasis in lean and obese states.

methodsThe actions of 20β-DHB on corticosteroid receptors in adipose tissue were investigated first using a combination of in silico, in vitro, and transcriptomic techniques and then in vivo administration in combination with receptor antagonists. Mice lacking one Cbr1 allele and mice overexpressing Cbr1 in their adipose tissue underwent metabolic phenotyping before and after induction of obesity with high-fat feeding.

results20β-DHB activated both the glucocorticoid and mineralocorticoid receptor in adipose tissue and systemic administration to wild-type mice induced glucose intolerance, an effect that was ameliorated by both glucocorticoid and mineralocorticoid receptor antagonism. Cbr1 haploinsufficient lean male mice had lower fasting glucose and improved glucose tolerance compared with littermate controls, a difference that was abolished by administration of 20β-DHB and absent in female mice with higher baseline adipose 20β-DHB concentrations than male mice. Conversely, overexpression of Cbr1 in adipose tissue resulted in worsened glucose tolerance and higher fasting glucose in lean male and female mice. However, neither Cbr1 haploinsfficiency nor adipose overexpression affected glucose dyshomeostasis induced by high-fat feeding.

conclusionsCarbonyl reductase 1 is a novel regulator of glucocorticoid and mineralocorticoid receptor activation in adipose tissue that influences glucose homeostasis in lean mice.

Indexed as

Adipose TissueAlcohol OxidoreductasesAnimalsCorticosteroneDiet, High-FatDisease Models, AnimalFemaleGene Knockdown TechniquesGlucocorticoidsGlucoseGlucose IntoleranceHEK293 CellsHomeostasisHumansMaleMice20-dihydrocorticosteroneAlcohol Oxidoreductasescarbonyl reductase 1, mouseCorticosteroneGlucocorticoidsGlucoseNR3C2 protein, humanReceptors, GlucocorticoidReceptors, MineralocorticoidCorticosteroneGlucocorticoidGlucocorticoid receptorGlucoseMetabolismMineralocorticoid receptorObesity

Identifiers

PMID33785425
PMCPMC8095185
OpenAlexW3146134563

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.