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ey0015.11-4 | New Developments in Monogenic Obesity | ESPEYB15

11.4 Early Childhood BMI Trajectories in Monogenic Obesity due to Leptin–, Leptin Receptor- and Melanocortin 4 Receptor Deficiency

K Kohlsdorf , A Nunziata , JB Funcke , S Brandt , J von Schnurbein , H Vollbach , B Lennerz , M Fritsch , S Greber-Platzer , E Fröhlich-Reiterer , M Lüdeke , G Borck , KM Debatin , P Fischer-Posovszky , M Wabitsch

To read the full abstract: Int J Obes (Lond). 2018 Feb 27.See comment on 11.7...

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ey0020.9-7 | Genetic Obesity and Genetic Risk Score | ESPEYB20

9.7. Rare antagonistic leptin variants and severe, early-onset obesity

JB Funcke , B Moepps , J Roos , J von Schnurbein , K Verstraete , E Frohlich-Reiterer , K Kohlsdorf , A Nunziata , S Brandt , A Tsirigotaki , A Dansercoer , E Suppan , B Haris , KM Debatin , SN Savvides , IS Farooqi , K Hussain , P Gierschik , P Fischer-Posovszky , M Wabitsch

Brief summary: The authors provide the first description of antagonistic hormone mutations as the cause of congenital disease in humans. The paper describes detailed characterizations of two novel, antagonistic leptin mutations underlying a formerly unrecognized form of congenital leptin dysfunction and delineate the challenges these mutations pose to the diagnosis and therapy of the disease.After the initial description of biologically inactive leptin v...

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ey0021.11-15 | Adipocyte Dysfunction and Obesity Related Comorbidities | ESPEYB21

11.15. A spatiotemporal proteomic map of human adipogenesis

F Klingelhuber , S Frendo-Cumbo , M Omar-Hmeadi , L Massier , P Kakimoto , AJ Taylor , M Couchet , S Ribicic , M Wabitsch , AC Messias , A Iuso , TD Muller , M Ryden , N Mejhert , N Krahmer

Brief Summary: This study created a temporally- and spatially-resolved proteomic atlas of human adipogenesis. It highlights cell restructuring and spatial reorganization of metabolic pathways to optimize cells for lipid accumulation and identifies C19orf12 as a differentiation-induced protein that regulates lipid storage in adipocytes.This study provides a comprehensive and detailed proteomic map that captures the dynamic changes in protein abundance and...

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ey0018.8-8 | Clinical Trials – New Treatments | ESPEYB18

8.8. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials

K Clement , E van den Akker , J Argente , A Bahm , WK Chung , H Connors , K De Waele , IS Farooqi , J Gonneau-Lejeune , G Gordon , K Kohlsdorf , C Poitou , L Puder , J Swain , M Stewart , G Yuan , M Wabitsch , P; Setmelanotide POMC and LEPR Phase 3 Trial Investigators Kuhnen

Lancet Diabetes Endocrinol. 2020 Dec;8(12):960970.https://pubmed.ncbi.nlm.nih.gov/33137293/This article reports the results of two single-arm, open-label, multicentre, phase 3 trials of the MC4R agonist, setmelanotide, in patients with severe obesity due to pro-opiomelanocortin (POMC) deficiency or leptin receptor (LEPR) deficiency. Mean % change in bodyweight after ~1 year was &#8722...

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ey0019.11-3 | New findings in adipose tissue biology | ESPEYB19

11.3. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis

Z Jiang , M Zhao , L Voilquin , Y Jung , MA Aikio , T Sahai , FY Dou , AM Roche , I Carcamo-Orive , JW Knowles , M Wabitsch , EA Appel , CL Maikawa , JP Camporez , GI Shulman , L Tsai , ED Rosen , CD Gardner , BM Spiegelman , KJ Svensson

katrinjs@stanford.edu Cell Metab 2021; 33(9): 18361852.e11http://www.ncbi.nlm.nih.gov/pubmed/34348115Brief Summary: This rodent study identified a novel adipokine in mice which triggers a signaling cascade similar to that of insulin. By acting via an unknown tyrosine kinase, isthmin-1 (ISM1) ameliorates metabolic disturbances associated wit...

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ey0021.11-14 | Adipocyte Dysfunction and Obesity Related Comorbidities | ESPEYB21

11.14. Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation

W Xia , P Veeragandham , Y Cao , Y Yayun Xu , TE Rhyne , J Qian , Hung Chao-Wei , P CHZhao , Y Jones , H Hui Gao , C Liddle , RT Yu , M Downes , RM Evans , M Ryden , M Wabitsch , Z Wang , H Hakozaki , J Schoneberg , SM Reilly , J Huang , AR Saltiel

Brief Summary: This study shows that obesity induces mitochondrial fragmentation and reduces oxidative capacity in white adipocytes through the activation of the small GTPase RalA. Targeted deletion of RalA in these cells prevents mitochondrial fragmentation, improves energy expenditure, and protects against obesity-induced metabolic dysfunctions, highlighting the critical role of RalA in obesity-related mitochondrial and metabolic abnormalities.Previous...

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ESPE Yearbook of Paediatric Endocrinology

11.4 Early Childhood BMI Trajectories in Monogenic Obesity due to Leptin–, Leptin Receptor- and Melanocortin 4 Receptor Deficiency

9.7. Rare antagonistic leptin variants and severe, early-onset obesity

11.15. A spatiotemporal proteomic map of human adipogenesis

8.8. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials

11.3. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis

11.14. Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation

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