Evidence map›Paper›PMID 32339772›Full record

ArticleMolecular metabolism2020

Metabolic insights from a GHSR-A203E mutant mouse model.

Lola J Torz, Sherri Osborne-Lawrence, Juan Rodriguez, Zhenyan He, María Paula Cornejo, Emilio Román Mustafá, Chunyu Jin, Natalia Petersen, Morten A Hedegaard, Maja Nybo and 8 more

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

18 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Loss-of-Function GHSR Variants Are Associated With Short Stature and Low IGF-I.The Journal of clinical endocrinology and metabolism · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Ghrelin receptor signaling in health and disease: a biased view.Trends in endocrinology and metabolism: TEM · 2023
    Review
  10. Article
  11. Binding Domain Characterization of Growth Hormone Secretagogue Receptor.Journal of translational internal medicine · 2022
    Article
  12. Review
  13. Review
  14. Article
  15. Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency.International journal of molecular sciences · 2021
    Review
  16. Review
  17. Article
  18. Ninjin'yoeito Targets Distinct CaFrontiers in nutrition · 2020
    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

18 authors at 3 institutions in 3 countries.

Lola J TorzDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Sherri Osborne-LawrenceCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Juan RodriguezCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Zhenyan HeCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
María Paula CornejoLaboratory of Neurophysiology, La Plata, Buenos Aires, Argentina.
Emilio Román MustafáLaboratory of Electrophysiology of the Multidisciplinary Institute of Cell Biology [Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA)], La Plata, Buenos Aires, Argentina.
Chunyu JinDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Natalia PetersenDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Morten A HedegaardDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Maja NyboNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Valentina Martínez DamonteLaboratory of Electrophysiology of the Multidisciplinary Institute of Cell Biology [Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA)], La Plata, Buenos Aires, Argentina.
Nathan P MetzgerCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Bharath K ManiCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Kevin W WilliamsCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Jesica RaingoLaboratory of Electrophysiology of the Multidisciplinary Institute of Cell Biology [Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA)], La Plata, Buenos Aires, Argentina.
Mario PerelloLaboratory of Neurophysiology, La Plata, Buenos Aires, Argentina.
Birgitte HolstDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. Electronic address: holst@sund.ku.dk.
Jeffrey M ZigmanCenter for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: jeffrey.zigman@utsouthwestern.edu.
Southwestern Medical Center · USUniversity of Copenhagen · DKConsejo Nacional de Investigaciones Científicas y Técnicas · AR

Funding

Ventromedial Hypothalamic Regulation of Metabolic Changes Induced by ExerciseP01DK119130 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI ELMQUIST, JOEL K. · 2019 to 2023
$10.0M
Role of the hormone LEAP2 in eating, body weight, blood glucose and survivalR01DK103884 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI ZIGMAN, JEFFREY M · 2015 to 2023
$3.4M
Cellular and Synaptic Reorganization after Exercise TrainingR01DK119169 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI WILLIAMS, KEVIN W · 2018 to 2021
$1.6M
NIDDK NIH HHS P01 DK119130NIDDK NIH HHS R01 DK103884NIDDK NIH HHS R01 DK119169
6 · The paper itself

Abstract

objectiveBinding of ghrelin to its receptor, growth hormone secretagogue receptor (GHSR), stimulates GH release, induces eating, and increases blood glucose. These processes may also be influenced by constitutive (ghrelin-independent) GHSR activity, as suggested by findings in short people with naturally occurring GHSR-A204E mutations and reduced food intake and blood glucose in rodents administered GHSR inverse agonists, both of which impair constitutive GHSR activity. In this study, we aimed to more fully determine the physiologic relevance of constitutive GHSR activity.

methodsWe generated mice with a GHSR mutation that replaces alanine at position 203 with glutamate (GHSR-A203E), which corresponds to the previously described human GHSR-A204E mutation, and used them to conduct ex vivo neuronal electrophysiology and in vivo metabolic assessments. We also measured signaling within COS-7 and HEK293T cells transfected with wild-type GHSR (GHSR-WT) or GHSR-A203E constructs.

resultsIn COS-7 cells, GHSR-A203E resulted in lower baseline IP

conclusionsOur data suggest that the A203E mutation ablates constitutive GHSR activity and that constitutive GHSR activity contributes to the native depolarizing conductance of GHSR-expressing arcuate NPY neurons. Although the A203E mutation does not block ghrelin-evoked signaling as assessed using in vitro and ex vivo models, GHSR-A203E mice lack the usual acute food intake response to administered ghrelin in vivo. The GHSR-A203E mutation also blunts GH release, and in aged mice leads to reduced body length and femur length, which are consistent with the short stature of human carriers of the GHSR-A204E mutation.

Indexed as

AllelesAmino Acid SubstitutionMutationAnimalsBody Weights and MeasuresCalcium SignalingCell LineElectrophysiological PhenomenaEnergy MetabolismGene Expression RegulationGene TargetingGenetic Association StudiesHEK293 CellsHormonesHumansHypothalamusHormonesReceptors, GhrelinConstitutive activityGHGhrelinGrowth hormone

Identifiers

PMID32339772
PMCPMC7242877
OpenAlexW3019705670

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.