ISSN 1662-4009 (online)

ey0018.10-14 | (1) | ESPEYB18

10.14. Targeted pharmacological therapy restores [beta]-cell function for diabetes remission

S Sachs , A Bastidas-Ponce , S Tritschler , M Bakhti , A Bottcher , MA Sanchez-Garrido , M Tarquis-Medina , M Kleinert , K Fischer , S Jall , A Harger , E Bader , S Roscioni , S Ussar , A Feuchtinger , B Yesildag , A Neelakandhan , CB Jensen , M Cornu , B Yang , B Finan , RD Di Marchi , MH Tschop , FJ Theis , SM Hofmann , TD Muller , H Lickert

Nature Metabolism. 2020;2(2):192–209. doi: 10.1038/s42255-020-0171-3.This experimental mouse study examined whether or not dedifferentiated β cells could be reversed or targeted by pharmacological intervention for diabetes remission. They identified evidence for β-cell dedifferentiation and dysfunction which could be reversed by single and combined pharmacological approach...

ey0018.11 | Martin Wabitsch, Daniel Tews, Julia von Schnurbein, Melanie Schirmer, Eleni Giannopoulou, Cem Süleyman Adiyaman, Christian Denzer, Stephanie Brandt | ESPEYB18

11. Obesity and Weight Regulation

Wabitsch Martin , Tews Daniel , von Schnurbein Julia , Schirmer Melanie , Giannopoulou Eleni , Adiyaman Cem Suleyman , Denzer Christian , Brandt Stephanie

PrefaceIn analogy to previous years, in this year’s chapter we can present only ~1% of the acquired publications according to our search criteria in Pubmed. The last year has again been extremely exciting for the field of obesity and weight regulation and it was a significant step into the future in terms of scientific output. Of course, one of the well-known phenomena of the past year has been a marked increase in child and adolescent body weights ...

ey0018.11-1 | The COVID 19 pandemic and obesity | ESPEYB18

11.1. Characteristics of hospitalized children with SARS-CoV-2 in the New York city metropolitan area

S Verma , R Lumba , HM Dapul , G Gold-von Simson , CK Phoon , JL Lighter , JS Farkas , A Vinci , A Noor , VN Raabe , D Rhee , M Rigaud , PV Mally , TM Randis , B Dreyer , AJ Ratner , CS Manno , A Chopra

Hosp Pediatr. 2021 Jan;11(1):71–78. 10.1542/hpeds.2020-001917. https://pubmed.ncbi.nlm.nih.gov/33033078/In a cohort of 82 children (0–21 years) who were hospitalised for severe SARS-CoV-2 associated respiratory illness, obesity was the strongest risk factor for the outcome of critical care. Already during the first COVID-19 wave...

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...

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...

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...

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...

ey0018.11-6 | New insight: neurobiology and weight regulation | ESPEYB18

11.6. Child neurobiology impacts success in family-based behavioral treatment for children with obesity

EA Schur , SJ Melhorn , K Scholz , MRB De Leon , CT Elfers , MG Rowland , BE Saelens , CL Roth

Int J Obes (Lond). 2020 Oct;44(10):2011–2022. 10.1038/s41366-020-0644-1. https://pubmed.ncbi.nlm.nih.gov/32713944/Schur et al. addressed the question, whether responsiveness to visual food cues in functional magnetic resonance imaging (fMRI) is related to the treatment success of a 6-month Family-based Behavioral Treatment (...

ey0018.11-7 | New insight: neurobiology and weight regulation | ESPEYB18

11.7. Genetic mapping of etiologic brain cell types for obesity

PN Timshel , JJ Thompson , TH Pers

eLife 2020;9:e55851. https://pubmed.ncbi.nlm.nih.gov/32955435/Timshel et al. describe a novel strategy for integrating single-cell RNA-sequencing (scRNA-seq) data with GWAS data on BMI associated genetic variants, and thereby identify 26 exclusively neuronal cell types that are significantly enriched for BMI heritability.The authors developed two scRNA-seq computation...

ey0018.11-8 | New treatment result: should bariatric surgery be done earlier in life? | ESPEYB18

11.8. Outcomes of bariatric surgery in older versus younger adolescents

SB Ogle , LC Dewberry , TM Jenkins , TH Inge , M Kelsey , M Bruzoni , JSA Pratt

Pediatrics 2021 Mar;147(3):e2020024182. 10.1542/peds.2020-024182 https://pubmed.ncbi.nlm.nih.gov/33526606/This sub-analysis of Teen-LABS study shows very similar improvements over 5 years after bariatric surgery between younger and older adolescents with severe obesity in %BMI change (−22.2% vs. −24.6%, respectively), resolution...