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Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity.
Funcke, Jan-Bernd; Moepps, Barbara; Roos, Julian; von Schnurbein, Julia; Verstraete, Kenneth; Fröhlich-Reiterer, Elke; Kohlsdorf, Katja; Nunziata, Adriana; Brandt, Stephanie; Tsirigotaki, Alexandra; Dansercoer, Ann; Suppan, Elisabeth; Haris, Basma; Debatin, Klaus-Michael; Savvides, Savvas N; Farooqi, I Sadaf; Hussain, Khalid; Gierschik, Peter; Fischer-Posovszky, Pamela; Wabitsch, Martin.
Affiliation
  • Funcke JB; From 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 Departme
  • Moepps B; From 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 Departme
  • Roos J; From 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 Departme
  • von Schnurbein J; From 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 Departme
  • Verstraete K; From 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 Departme
  • Fröhlich-Reiterer E; From 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 Departme
  • Kohlsdorf K; From 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 Departme
  • Nunziata A; From 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 Departme
  • Brandt S; From 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 Departme
  • Tsirigotaki A; From 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 Departme
  • Dansercoer A; From 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 Departme
  • Suppan E; From 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 Departme
  • Haris B; From 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 Departme
  • Debatin KM; From 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 Departme
  • Savvides SN; From 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 Departme
  • Farooqi IS; From 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 Departme
  • Hussain K; From 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 Departme
  • Gierschik P; From 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 Departme
  • Fischer-Posovszky P; From 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 Departme
  • Wabitsch M; From 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 Departme
N Engl J Med ; 388(24): 2253-2261, 2023 Jun 15.
Article in En | MEDLINE | ID: mdl-37314706
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.).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Obesity, Morbid / Leptin Limits: Child / Humans Language: En Journal: N Engl J Med Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Obesity, Morbid / Leptin Limits: Child / Humans Language: En Journal: N Engl J Med Year: 2023 Document type: Article