ArticleThe New England journal of medicine2023
Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity.
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Article in The New England journal of medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
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21citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% of its field
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Classification of Congenital Leptin Deficiency.The Journal of clinical endocrinology and metabolism · 2024Pooled it
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic obesity.Reviews in endocrine & metabolic disorders · 2026Review
- Management of Childhood Obesity.International journal of molecular sciences · 2026Review
- Structural and functional characterization of the Pro64Ser leptin mutant: Implications for congenital leptin deficiency.Biophysical journal · 2025Article
- Body weight regulation models in humans: insights for testing their validity.Nature reviews. Endocrinology · 2025Review
- IMPROVE 2023: The 2nd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2025Article
- Antiobesity Pharmacotherapy for Patients With Genetic Obesity Due to Defects in the Leptin-Melanocortin Pathway.Endocrine reviews · 2025Review
- Clinical symptoms and epidemiological survey of early-onset severe obesity among children and adolescents.Pakistan journal of medical sciences · 2025Article
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Anti-Obesity Medication in the Management of Children and Adolescents With Obesity: Recent Developments and Research Gaps.Clinical endocrinology · 2025Review
- A real-world pharmacovigilance assessment and literature review of lymphoma development in lipodystrophy.Frontiers in endocrinology · 2025Review
- Unraveling the genetic links between obesity or insulin resistance and breast cancer through the impact of CD295 and ITLN1 SNPs with DNA damage in a case-controlled study with bioinformatics analysis.Frontiers in medicine · 2025Article
- The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood.BMC medicine · 2024Article
- Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity.Current obesity reports · 2024Review
- A quantitative pipeline to assess secretion of human leptin coding variants reveals mechanisms underlying leptin deficiencies.The Journal of biological chemistry · 2024Article
- Leptin receptor deficiency impedes metabolic surgery related-weight loss through inhibition of energy expenditure in db/db mice.Diabetology & metabolic syndrome · 2024Article
- Leptin Reduction as a Required Component for Weight Loss.Diabetes · 2024Article
- Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide.Frontiers in endocrinology · 2024Article
- Unravelling leptin variants: advancing precision medicine in obesity.Nature reviews. Endocrinology · 2023Article
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Authors and funding
20 authors at 1 institution in 7 countries.
Jan-Bernd FunckeFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).ORCID 0000-0002-2596-3167
Barbara MoeppsFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Julian RoosFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).ORCID 0000-0003-2105-6671
Julia von SchnurbeinFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Kenneth VerstraeteFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Elke Fröhlich-ReitererFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Katja KohlsdorfFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Adriana NunziataFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Stephanie BrandtFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Alexandra TsirigotakiFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Ann DansercoerFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Elisabeth SuppanFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Basma HarisFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Klaus-Michael DebatinFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Savvas N SavvidesFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
I Sadaf FarooqiFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Khalid HussainFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).ORCID 0000-0002-5480-7112
Peter GierschikFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).
Pamela Fischer-PosovszkyFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).ORCID 0000-0003-3402-9840
Martin WabitschFrom the Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine (J.-B.F., J.R., J.S., K.K., A.N., S.B., P.F.-P., M.W.), the Institute of Experimental and Clinical Pharmacology, Toxicology, and Pharmacology of Natural Products (B.M., P.G.), and the Department of Pediatrics and Adolescent Medicine (K.-M.D.), Ulm University Medical Center, Ulm, Germany; the Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas (J.-B.F.); the Unit for Structural Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium (K.V., A.T., A.D., S.N.S.); the Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria (E.F.-R., E.S.); the Division of Endocrinology, Department of Pediatrics, Sidra Medicine, Doha, Qatar (B.H., K.H.); and Wellcome Trust-Medical Research Council Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom (I.S.F.).ORCID 0000-0001-6795-8430
Universität Ulm · DE
Funding
Wellcome Trust 207462/Z/17/Z
Abstract
Hormone absence or inactivity is common in congenital disease, but hormone antagonism remains controversial. Here, we characterize two novel homozygous leptin variants that yielded antagonistic proteins in two unrelated children with intense hyperphagia, severe obesity, and high circulating levels of leptin. Both variants bind to the leptin receptor but trigger marginal, if any, signaling. In the presence of nonvariant leptin, the variants act as competitive antagonists. Thus, treatment with recombinant leptin was initiated at high doses, which were gradually lowered. Both patients eventually attained near-normal weight. Antidrug antibodies developed in the patients, although they had no apparent effect on efficacy. No severe adverse events were observed. (Funded by the German Research Foundation and others.).
Indexed as
LeptinObesity, MorbidAntibodiesChildHomozygoteHumansSignal TransductionAntibodiesLeptin
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