hrp0086fc13.2 | Management of Obesity | ESPE2016

Measurement of Immunofunctional Leptin to Detect Patients with Functional Leptin Deficiency

Wabitsch Martin , Pridzun Lutz , Ranke Michael , Flehmig Bertram , Fischer-Posovszky Pamela , Moss Anja , Schaab Michael , von Schnurbein Julia , Kratzsch Jurgen

Background: Recently, patients with severe obesity have been described due to functional leptin deficiency. This new entity is characterized by high immunoreactive levels of circulating leptin (Lep), but a reduced bioactivity of the hormone due to defective receptor binding (N Engl J Med 2015;372:48–54). Since these patients can be successfully treated with human recombinant leptin (metreleptin), a diagnostic tool to detect functional leptin deficiency is needed.<p cl...

hrp0082fc8.3 | Fat Metabolism | ESPE2014

Identification of Death Ligand TNF-Related Apoptosis-Inducing Ligand as a Potent Mitogen in Human Preadipocytes

Funcke Jan-Bernd , Zoller Verena , El Hay Muad Abd , Debatin Klaus-Michael , Wabitsch Martin , Fischer-Posovszky Pamela

Background: Adipose tissue is an important endocrine organ. Its secretion profile is robustly changed in the context of obesity fueling the development of comorbidities such as insulin resistance, diabetes mellitus type 2, and atherosclerosis. We have recently shown that the adipose tissue expression of the death ligand TNF-Related Apoptosis-Inducing Ligand TRAIL and its receptors is upregulated in obesity.Objective and Hypotheses: In this project, we in...

hrp0082p1-d1-103 | Fat Metabolism &amp; Obesity | ESPE2014

TNF-Related Apoptosis-Inducing Ligand Induces a Pro-Inflammatory Secretion Profile in Human Adipocytes

Zoller Verena , El Hay Muad Abd , Funcke Jan-Bernd , Debatin Klaus-Michael , Wabitsch Martin , Fischer-Posovszky Pamela

Background: Obesity is tightly associated with adipose tissue inflammation. Tumor necrosis factor-alpha (TNFα) has been identified as a key player in this inflammatory process and has been linked to the development of obesity-associated insulin resistance. Our group studies the involvement of TNF superfamily members in obesity-induced alterations in adipose tissue.Objective and hypotheses: Here, we aimed to identify the effects of the TNF superfamil...

hrp0084p1-67 | Fat | ESPE2015

miR-146a-Mediated Suppression of the Inflammatory Response in Human Adipocytes

Roos Julian , Enlund Eveliina , Tews Daniel , Funcke Jan-Bernd , Zoller Verena , Debatin Klaus-Michael , Wabitsch Martin , Fischer-Posovszky Pamela

Background: microRNAs (miRNAs) are a class of small (18–25 nucleotides), non-coding RNA molecules. They play an important role in the regulation of gene expression by either suppressing translation of genes or inducing their mRNA degradation. Several miRNA species are expressed in adipose tissue and involved in adipocyte function.Objective and hypotheses: Obesity leads to the infiltration of macrophages into adipose tissue causing local inflammation...

hrp0097fc14.4 | Late Breaking | ESPE2023

Improvement in insulin sensitivity and glucose metabolism in adolescents with obesity treated with once-weekly semaglutide 2.4 mg: a secondary analysis of the STEP TEENS trial

Arslanian Silva , Goldman Bryan , Gies Inge , M. Harder-Lauridsen Nina , Karlsson Tobias , Kelly Aaron , Wabitsch Martin , Weghuber Daniel

Obesity in adolescents is associated with increased risk of prediabetes and type 2 diabetes (T2D) and long-term complications in adulthood. Data regarding the effects of anti-obesity medications on glycaemic outcomes in adolescents are sparse. STEP TEENS (NCT04102189), a phase 3a, double-blind, placebo-controlled randomised trial in adolescents 12 to <18 years of age with obesity demonstrated that once-weekly subcutaneous semaglutide 2.4 mg provided a greater percentage red...

hrp0092rfc11.5 | Pituitary, Neuroendocrinology and Puberty Session 2 | ESPE2019

IGF-1 Serum Concentrations and Growth in Children with Congenital Leptin Deficiency (CLD) Before and After Replacement Therapy with Metreleptin

Beghini Marianna , von Schnurbein Julia , Körber Ingrid , Brandt Stephanie , Kohlsdorf Katja , Vollbach Heike , Lennerz Belinda , Denzer Christian , Wabitsch Martin

Background: Leptin, primarily secreted by adipocytes, is a pivotal signal of the body's energy status and exhibits pleiotropic effects. Homozygous mutations in the leptin gene which result in defective synthesis, release or bioactivity, cause intense hyperphagia and early-onset severe obesity, along with multiple metabolic, hormonal, and immunological abnormalities. In vitro and animal model studies suggest that leptin plays a role in linear growth. So far...

hrp0089rfc6.4 | Fat, Metabolism and Obesity | ESPE2018

Functionality and Phenotypic Characteristics of Mutations in the Human Leptin Receptor

Nunziata Adriana , Funcke Jan-Bernd , Borck Guntram , von Schnurbein Julia , Lennerz Belinda , Moepps Barbara , Gierschik Peter , Fischer-Posovszky Pamela , Wabitsch Martin

Objective: Merge and standardize the scarce data on molecular and phenotypic findings of mutations in the human leptin receptor (LEPR) gene causing a rare form of severe early-onset obesity.Methods: We summarized functional and phenotypic traits of LEPR mutations reported in the literature in a structured and comprehensive manner. Additional data was obtained from 6 subjects of our outpatient clinic not reported so far. Functionality of mutations was ass...

hrp0089p2-p141 | Fat, Metabolism and Obesity P2 | ESPE2018

Associations between Total Leptin, Bio-inactive Leptin, Soluble Leptin Receptor and Anthropometrics in Children with Severe Early-onset Obesity (SEOO) – the German-Polish Study (EOL-GPS)

Zachurzok Agnieszka , Malecka-Tendera Ewa , Petriczko Elzbieta , Mazur Artur , Pridzun Lutz , Flehmig Bertram , Schnurbein Julia von , Ranke Michael B. , Wabitsch Martin , Brandt Stephanie

Background: Severe early-onset obesity (SEOO) in children is more frequently observed in subjects with genetic disorders of which those of leptin pathway can be analyzed biochemically and genetically.Objectives: The aim of the study was to investigate anthropometrics and leptin parameters, specifically searching for bio-inactive leptin, in children with SEOO.Methods: Study cohort includes children ...

hrp0086p1-p194 | Diabetes P1 | ESPE2016

Longitudinal Monitoring of Pediatric Insulin Treatment in Germany and Austria: Age-Dependent Analysis of 63 967 Children and Adolescents with Type 1 Diabetes from the DPV Registry

Bohn Barbara , Karges Beate , Vogel Christian , Otto Klaus-Peter , Marg Wolfgang , Hofer Sabine E , Frohlich-Reiterer Elke , Holder Martin , Plamper Michaela , Wabitsch Martin , Kerner Wolfgang , Holl Reinhard W

Background: Depending on age, needs and preferences in insulin therapy strongly differ between children and adolescents with type 1 diabetes (T1D).Objective and hypotheses: To analyse trends in insulin regimen and type of insulin used over the last two decades in three age-groups of pediatric patients with T1D from Germany/Austria.Method: 63 967 subjects (<18 year of age) with T1D documented between 1995 and 2014 from the &#145...

hrp0082p1-d1-109 | Fat Metabolism &amp; Obesity | ESPE2014

Identification of Brown Adipocyte Progenitor Marker Genes in Progenitor Cells from Human Deep Neck and Subcutaneous Adipose Tissue by Gene Array Analysis

Tews Daniel , Schwar Verena , Weber Theresia , Scheithauer Marc , Fromme Tobias , Klingenspor Martin , Barth Thomas F , Moller Peter , Fischer-Posovszky Pamela , Wabitsch Martin

Background: Studies in animal models revealed that brown and white adipocytes derive from different progenitor cells. Molecular characteristics of these cells have not been investigated in detail in humans.Objective and hypotheses: To identify novel markers of human brown adipocyte progenitor cells.Method: Progenitor cells from human paired deep neck and subcutaneous adipose tissue samples were obtained from n=12 subjects ...