| Title: |
Cross-species studies implicate the melanocortin 3 receptor more strongly in the control of pubertal development than energy balance. |
| Authors: |
Duckett, Katie; McClellan, Alyce; Corbin, Laura J; Cimino, Irene; Elhakeem, Ahmed; Goncalves Soares, Ana; Williamson, Alice; Cross, Eloise; Fairhurst-Hunter, Zammy; Petrovski, Slavé; Rimmington, Debra; Alegre-Díaz, Jesús; Berumen, Jaime; Kuri-Morales, Pablo; Tapia-Conyer, Roberto; BELIEVE study; Mokrosinski, Jacek; Farooqi, I Sadaf; Rasheed, Asif; Saleheen, Danish; Butterworth, Adam S; Timpson, Nicholas J; Coll, Anthony P; Raffan, Eleanor; Lam, Brian YH; O'Rahilly, Stephen |
| Publisher Information: |
Elsevier; Department of Clinical Biochemistry; //doi.org/10.1016/j.molmet.2025.102301 |
| Publication Year: |
2026 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
ALSPAC; MC3R; Melanocortins; Obesity; Puberty; Animals; Receptor; Melanocortin; Type 3; Female; Mice; Male; Humans; Energy Metabolism; Dogs; Adolescent; Child; Sexual Maturation; Body Mass Index; Body Composition |
| Description: |
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 |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/393501; https://doi.org/10.17863/CAM.123818 |
| DOI: |
10.17863/CAM.123818 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/393501; https://doi.org/10.17863/CAM.123818 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.B550868B |
| Database: |
BASE |