Your browser doesn't support javascript.
loading
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.
Afiliación
  • 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 en En | MEDLINE | ID: mdl-37314706
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.).
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obesidad Mórbida / Leptina Límite: Child / Humans Idioma: En Revista: N Engl J Med Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obesidad Mórbida / Leptina Límite: Child / Humans Idioma: En Revista: N Engl J Med Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos