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Record W4417212921 · doi:10.1016/j.molmet.2025.102301

Cross-species studies implicate the melanocortin 3 receptor more strongly in the control of pubertal development than energy balance

2025· article· en· W4417212921 on OpenAlexaboutno aff
Katie Duckett, Alyce McClellan, Laura J. Corbin, Irène Cimino, Ahmed Elhakeem, Ana Gonçalves Soares, Alice Williamson, Eloise Cross, Zammy Fairhurst-Hunter, Slavé Petrovski, Debra Rimmington, Jesús Alegre-Díaz, Jaime Berúmen, Pablo Kuri‐Morales, Roberto Tapia‐Conyer, Jacek Mokrosiński, I. Sadaf Farooqi, Asif Rasheed, Danish Saleheen, Adam S. Butterworth, Nicholas J. Timpson, Anthony P. Coll, Eleanor Raffan, Brian Lam, Stephen O’Rahilly

Bibliographic record

VenueMolecular Metabolism · 2025
Typearticle
Languageen
FieldNeuroscience
TopicRegulation of Appetite and Obesity
Canadian institutionsnot available
FundersNIHR Cambridge Biomedical Research CentreBiotechnology and Biological Sciences Research CouncilMedical Research CouncilWellcome Trust
KeywordsMelanocortinMelanocortin receptorMelanocortin 3 receptorMissense mutationAppetiteObesityReceptorEnergy balanceBody mass index

Abstract

fetched live from OpenAlex

. We detected a canine MC3R missense variant (p.M320I) which is common in labrador retrievers and showed that this significantly impairs receptor signalling. Dogs homozygous for p.M320I were lighter and showed delayed pubertal development but were not significantly more obese than wild-type or heterozygous dogs. We also established that the lack of Mc3r delayed pubertal development in both male and female mice. Finally, we studied growth and pubertal trajectories of individuals carrying rare loss-of-function MC3R variants and found that male carriers had delayed peak weight velocity and genital development but had no evidence for excess body fat compared to non-carriers. Our results support MC3R having a conserved role across mammals in controlling growth and pubertal timing. While MC3R deficiency may influence linear growth and body composition, complete loss of MC3R does not result in a penetrant human obesity syndrome.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.282
Threshold uncertainty score0.399

Codex and Gemma teacher scores by category

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 science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.018
GPT teacher head0.287
Teacher spread0.269 · 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 teacher head, 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

Citations3
Published2025
Admission routes1
Has abstractyes

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