Evidence map›Paper›PMID 26976589›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism.

Fantao Meng, Yong Han, Dollada Srisai, Valery Belakhov, Monica Farias, Yong Xu, Richard D Palmiter, Timor Baasov, Qi Wu

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 64 citations in OpenAlex.

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  14. Role of the gut-brain axis in energy and glucose metabolism.Experimental & molecular medicine · 2022
    Review
  15. The critical role of gut microbiota in obesity.Frontiers in endocrinology · 2022
    Review
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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

9 authors at 4 institutions in 2 countries.

Fantao MengChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;
Yong HanChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;
Dollada SrisaiDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242;
Valery BelakhovSchulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel;
Monica FariasChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;
Yong XuChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;
Richard D PalmiterDepartment of Biochemistry, University of Washington, Seattle, WA 98195; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 qiw@bcm.edu palmiter@uw.edu.
Timor BaasovSchulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel;
Qi WuChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030; qiw@bcm.edu palmiter@uw.edu.
Children's Nutrition Research Center at Baylor College of Medicine · USTechnion – Israel Institute of Technology · ILHoward Hughes Medical Institute · USUniversity of Iowa · US

Funding

Effect of Killing or Removing GABA from NPY/AgRP NeuronsR01DA024908 · NIDA · UNIVERSITY OF WASHINGTON · PI PALMITER, RICHARD D. · 2007 to 2021
$3.5M
CNS Circuits Mediating Estrogenic Regulation on Energy and Glucose HomeostasisR01DK093587 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI XU, YONG · 2011 to 2015
$1.6M
Targeting hypothalamic steroid receptor co-activator-1 to treat obesityR01DK101379 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI XU, YONG · 2014 to 2017
$1.2M
A Novel AgRP Neurons to the Dorsal Raphe Circuit in Control of Energy ExpenditureR56DK109194 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI WU, QI · 2016 to 2016
$105k
Howard Hughes Medical InstituteNIDA NIH HHS R01 DA024908NIDA NIH HHS R01-DA24908NIDDK NIH HHS R01 DK093587NIDDK NIH HHS R01DK093587NIDDK NIH HHS R01 DK101379NIDDK NIH HHS R01DK101379NIDDK NIH HHS R56 DK109194
6 · The paper itself

Abstract

Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes.

Indexed as

Agouti-Related ProteinAnimalsEnergy MetabolismFeeding Behaviorgamma-Aminobutyric AcidGenetic EngineeringGlutamate DecarboxylaseHypothalamusMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicSignal TransductionAgouti-Related ProteinAgrp protein, mousegamma-Aminobutyric AcidGlutamate Decarboxylaseglutamate decarboxylase 1glutamate decarboxylase 2AgRP neuronseating disordersfeeding behaviorGABAinducible gene knockout

Identifiers

PMID26976589
PMCPMC4822580
OpenAlexW2298806098

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.