New hope: Increased diagnostic yield for disease causing MC4R variants and pharmacological treatment options

ey0018.11-2 | New hope: Increased diagnostic yield for disease causing MC4R variants and pharmacological treatment options | ESPEYB18

11.2. Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signalling

H Israeli , O Degtjarik , F Fierro , V Chunilal , AK Gill , NJ Roth , J Botta , V Prabahar , Y Peleg , LF Chan , D Ben-Zvi , PJ McCormick , Y Niv , M Shalev-Benami

Science 2021;372(6544): 808–814 doi: https://doi.org/10.1126/science.abf7958Isreali et al. describe the molecular structure of the melanocortin 4 receptor (MC4R) complexed with its effector G protein (Gs alpha) and setmelanotide, a pharmacological agonist of MC4R.MC4R is a known key element in body weight regulation, connecting response to leptin with inhibition o...

0 shares

ey0018.11-3 | New hope: Increased diagnostic yield for disease causing MC4R variants and pharmacological treatment options | ESPEYB18

11.3. Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation

B Brouwers , EM de Oliveira , M Marti-Solano , FBF Monteiro , SA Laurin , JM Keogh , E Henning , R Bounds , CA Daly , S Houston , V Ayinampudi , N Wasiluk , D Clarke , B Plouffe , M Bouvier , MM Babu , IS Farooqi , J Mokrosiński

J Cell Rep. 2021 Mar 23;34(12):108862. 10.1016/j.celrep.2021.108862. https://pubmed.ncbi.nlm.nih.gov/33761344/This study demonstrates that MC4R variants found in humans affect receptor endocytosis, trafficking and dimerization and thus reveal multiple cellular mechanisms involved in weight regulation. The findings contributes to our und...

0 shares

ey0018.11-4 | New hope: Increased diagnostic yield for disease causing MC4R variants and pharmacological treatment options | ESPEYB18

11.4. Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort

KH Wade , BYH Lam , A Melvin , W Pan , LJ Corbin , DA Hughes , K Rainbow , JH Chen , K Duckett , X Liu , J Mokrosiński , A Morseburg , S Neaves , A Williamson , C Zhang , IS Farooqi , GSH Yeo , NJ Timpson , S O'Rahilly

Nat Med, 2021 Jun;27(6):1088–1096. 10.1038/s41591-021-01349-y. https://pubmed.ncbi.nlm.nih.gov/34045736/This paper reports the high prevalence of MC4R loss-of-function (LoF) variants in a normal population and their large impact on longitudinally assessed anthropometric traits from birth to young adult life.Th...

0 shares

ey0018.11-5 | New hope: Increased diagnostic yield for disease causing MC4R variants and pharmacological treatment options | ESPEYB18

11.5. Obesity treatment effect in danish children and adolescents carrying melanocortin-4 receptor mutations

C Trier , M Hollensted , TM Schnurr , MAV Lund , TRH Nielsen , G Rui , EA Andersson , M Svendstrup , DS Bille , AP Gjesing , CE Fonvig , C Frithioff-Bojsoe , M Balslev-Harder , S Quan , M Gamborg , O Pedersen , L Angquist , JC Holm , T Hansen

Int J Obes (Lond). 2021;45(1):66–76. doi: https://doi.org/10.1038/s41366-020-00673-6This study investigated the influence of MC4R variants on treatment effectiveness in a large cohort undergoing an outpatient treatment program. Carriers of MC4R loss-of-function (LoF) variants showed a lack of improvement in BMI, in contrast to non LoF carriers.As we learn th...

0 shares

ESPE Yearbook of Paediatric Endocrinology

Yearbook of Paediatric Endocrinology 2021

11. Obesity and Weight Regulation

11.2. Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signalling

11.3. Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation

11.4. Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort

11.5. Obesity treatment effect in danish children and adolescents carrying melanocortin-4 receptor mutations

BiosciAbstracts