Evidence map›Paper›PMID 41386534›Full record

ArticleMolecular metabolism2026

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

Katie Duckett, Alyce McClellan, Laura J Corbin, Irene Cimino, Ahmed Elhakeem, Ana Goncalves Soares, Alice Williamson, Eloise Cross, Zammy Fairhurst-Hunter, Slavé Petrovski and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026
    Review
  2. Review
  3. Article
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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

26 authors.

Katie DuckettMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Alyce McClellanDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Laura J CorbinMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Irene CiminoMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Ahmed ElhakeemMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Ana Goncalves SoaresMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Alice WilliamsonMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Eloise CrossMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Zammy Fairhurst-HunterCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Slavé PetrovskiCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Debra RimmingtonMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Jesús Alegre-DíazExperimental Medicine Unit from the Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Jaime BerumenExperimental Medicine Unit from the Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Pablo Kuri-MoralesExperimental Medicine Unit from the Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico; Instituto Tecnológico y de Estudios Superiores de Monterrey, Tecnológico, Monterrey, Nuevo León, Mexico.
Roberto Tapia-ConyerExperimental Medicine Unit from the Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
BELIEVE study,
Jacek MokrosinskiMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
I Sadaf FarooqiMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Asif RasheedCenter for Non-Communicable Diseases, Karachi, Pakistan.
Danish SaleheenCenter for Non-Communicable Diseases, Karachi, Pakistan; Columbia University Irving Medical Center, New York, NY, USA.
Adam S ButterworthBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Nicholas J TimpsonMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Anthony P CollMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Eleanor RaffanMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Electronic address: er311@cam.ac.uk.
Brian Y H LamMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK. Electronic address: yhbl2@cam.ac.uk.
Stephen O'RahillyMedical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK. Electronic address: so104@cam.ac.uk.

Funding

Department of Health NIHR203312Wellcome Trust 205187Wellcome Trust 207462Wellcome Trust 314234
6 · The paper itself

Abstract

Hypothalamic neurons expressing either POMC or AGRP sense nutritional state directly and indirectly and transmit these neuropeptide signals to other brain centres through the melanocortin 3 and 4 receptors. MC4R is primarily concerned with the control of appetite and energy expenditure while MC3R is more closely related to the control of linear growth and the timing of puberty. The role of MC3R in the long-term control of energy balance and body composition is less clear, particularly in humans. We have undertaken studies in humans, domestic dogs and mice with the goal of clarifying the relative impact of MC3R deficiency on energy balance, growth and sexual development. By studying three large consanguineously enriched cohorts, totalling approximately 300K people, we identified nine individuals who are homozygous for functionally null MC3R variants. The body mass index (BMI) of the homozygous MC3R variant carriers was not significantly different from that of age, sex and demographically matched controls, with six of the nine homozygotes having a BMI <30 kg/m

Indexed as

Energy MetabolismPubertyReceptor, Melanocortin, Type 3AdolescentAnimalsBody CompositionBody Mass IndexChildDogsFemaleHumansMaleMiceSexual MaturationMC3R protein, humanReceptor, Melanocortin, Type 3ALSPACMC3RMelanocortinsObesityPuberty

Identifiers

PMID41386534
PMCPMC12808844

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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.