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Record W3127462604 · doi:10.1016/j.cmet.2021.01.015

The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling

2021· article· en· W3127462604 on OpenAlexafffund
Qian Zhang, Robert Augustin, Mostafa Bakhti, Gustav Colldén, Daniel J. Drucker, Annette Feuchtinger, Cristina García Cáceres, Gerald Grandl, Alexandra Harger, Stephan Herzig, Susanna M. Hofmann, Cassie Holleman, Martin Jastroch, Susanne Keipert, Maximilian Kleinert, Patrick J. Knerr, Konxhe Kulaj, Beata Legutko, Heiko Lickert, Xue Liu, Gerd Luippold, Dominik Lutter, Emilija Malogajski, Marta Tarquis-Medina, Stephanie A. Mowery, Andreas Blutke, Diego Pérez–Tilve, Ciro Salinno, Laura Sehrer, Richard D. DiMarchi, Matthias H. Tschöp, Kerstin Stemmer, Brian Finan, Christian Wolfrum, Timo D. Müller

Bibliographic record

VenueCell Metabolism · 2021
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsLunenfeld-Tanenbaum Research InstituteUniversity of Toronto
FundersEuropean Research CouncilCanadian Institutes of Health ResearchBanting and Best Diabetes Centre, University of TorontoMenarini GroupHelmholtz AssociationIndiana UniversityAlexander von Humboldt-StiftungNovo NordiskMerck KGaABoehringer IngelheimDeutsche ForschungsgemeinschaftEli Lilly and Company
KeywordsEndocrinologyInternal medicineFood intakeBody weightBiologyGastric inhibitory polypeptideMedicineHormoneGlucagon

Abstract

fetched live from OpenAlex

Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for the treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but the physiological relevance of CNS Gipr remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin mice with CNS-hGIPR deletion show decreased body weight and improved glucose metabolism. In DIO mice, acute central and peripheral administration of acyl-GIP increases cFos neuronal activity in hypothalamic feeding centers, and this coincides with decreased body weight and food intake and improved glucose handling. Chronic central and peripheral administration of acyl-GIP lowers body weight and food intake in wild-type mice, but shows blunted/absent efficacy in CNS-Gipr KO mice. Also, the superior metabolic effect of GLP-1/GIP co-agonism relative to GLP-1 is extinguished in CNS-Gipr KO mice. Our data hence establish a key role of CNS Gipr for control of energy metabolism.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.208
Teacher spread0.200 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations298
Published2021
Admission routes2
Has abstractyes

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