hrp0092p2-110 | Fat, Metabolism and Obesity | ESPE2019

Pubertal Milestones and Related Hormonal Changes Among Children with Obesity

Stein Robert , Kempf Elena , Gesing Julia , Stanik Juraj , Kiess Wieland , Körner Antje

Background and Objective: Obesity is known to affect pubertal timing. However, existing data are still controversial, observing either delayed or accelerated pubertal onset, especially among boys. Herein, we evaluated pubertal milestones and underlying hormonal changes between lean and obese children.Material and Methods: We examined 13,484 events from 4,855 lean (BMI SDS <1.28) and 1,983 obese (BMI SDS > 1.88) c...

hrp0089fc6.3 | Fat, Metabolism and obesity | ESPE2018

Role of PTEN in the Proliferation and Differentiation of Preadipocytes

Kirstein Anna , Kassner Franziska , Schmid Gordian L. , Handel Norman , Penke Melanie , Kiess Wieland , Garten Antje

Background/aim: The PTEN hamartoma tumor syndrome (PHTS) is an overgrowth syndrome caused mainly by germline mutations in the tumor suppressor PTEN. Patients are predisposed for the development of malignant and benign tumors. Children and adolescents with PHTS frequently develop single or multiple lipomas. PTEN antagonizes the phosphatidylinositide3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway, which promotes proliferation and differentiation in ...

hrp0089p1-p093 | Fat, Metabolism and Obesity P1 | ESPE2018

Functional Characterization of Novel and Known Genetic Variants in the Leptin Receptor (LEPR) Gene of Two Patients with Morbid Obesity

Voigtmann Franziska , Robert Stein , Landgraf Kathrin , Abou Jamra Rami , Kiess Wieland , Korner Antje

Background: The leptin signaling cascade is a crucial regulator of satiety and energy homeostasis in the hypothalamus, comprising extracellular leptin binding to its receptor, phosphorylation and nuclear translocation of STAT3 (signal transducer and activator of transcription 3) and consecutively the generation of a central satiety signal via neuropeptide secretion. We identified three variants in the extracellular domains of the LEPR gene in two children with severe ...

hrp0089p2-p170 | Fat, Metabolism and Obesity P2 | ESPE2018

Development of Resistance to Sorafenib, a Multikinase Inhibitor, in Hepatocellular Carcinoma is Mediated by SIRT

Garten Antje , Grohmann Theresa , Barnikol-Oettler Anja , Kluckova Katharina , Lavery Gareth , Kiess Wieland , Penke Melanie

Background/aim: Sorafenib® is a multi-kinase inhibitor and one of the few systemic treatment options for patients with advanced hepatocellular carcinomas (HCCs). Resistance to Sorafenib® develops frequently and could be mediated by the NAD dependent deacetylase sirtuin (SIRT) 1, a master regulator of cellular energy metabolism and stress responses. We aimed to find out if Sorafenib® treatment depends on changes in cellular NAD le...

hrp0089p2-p398 | Thyroid P2 | ESPE2018

Diagnosis and Clinical Course of Amiodarone Induced Hyperthyroidism in Three Adolescent Patients

Gesing Julia , Hoppmann Julia , Gebauer Roman , Pfaffle Roland , Bertsche Astrid , Kiess Wieland

Amiodarone induced hyperthyroidism is a known side effect of amiodarone treatment. In the pediatric population long-term amiodarone treatment is rarely indicated because of its severe side effects including thyroid function impairment and therefore treatment is restricted to therapy resistant arrhythmias. In the literature scarce data is available on management and therapy of amiodarone induced thyroid dysfunction at a young age. We present three adolescent patients developin...

hrp0086p1-p446 | Fat Metabolism and Obesity P1 | ESPE2016

Bioinactive Leptin is not Frequently Detected in Severe Early Onset Childhood Obesity

Stanik Juraj , Kratzsch Jurgen , Scheuermann Kathrin , Gašperikova Daniela , Kiess Wieland , Korner Antje

Background: Rodent models of leptin inactivity show progressive obesity due to exaggerated food intake. In humans, only rare monogenic cases of leptin deficiency and almost absent circulating leptin levels have been identified. Recently, two cases of children with early onset massive obesity due to biofunctionally inactive leptin in the face of normal total levels have been identified.Objective and hypotheses: Here we aimed to identify leptin inactivity ...

hrp0086p2-p708 | Endocrinology and Multisystemic Diseases P2 | ESPE2016

Inhibition of NAMPT Increases the Sensitivity of Leukemia Cells for Etoposide

Gorski Theresa , Petzold-Quinque Stefanie , Richter Sandy , Schuster Susanne , Penke Melanie , Kiess Wieland , Garten Antje

Background: Cancer cells have a high NAD turnover rate due to their increased cell proliferation and DNA repair. Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the NAD salvage pathway, a regulator of the intracellular NAD pool and of the activity of Sirtuins (SIRTs), a class of NAD-dependent deacetylases.Objective and hypotheses: Cancer cells are highly dependent on NAD and are expected to be more susceptible to an inhibition of NAD ...

hrp0086p2-p857 | Syndromes: Mechanisms and Management P2 | ESPE2016

A Case of Familial Silver-Russell Syndrome

Hoppmann Julia , Netchine Irene , Eggermann Thomas , Jamra Rami Abou , Kiess Wieland , Pfaffle Roland

Background: Silver-Russell syndrome (SRS) is a heterogeneous condition characterized by intrauterine growth restriction, relative macrocephaly at birth, postnatal growth retardation, body asymmetry, feeding difficulties/ low body mass index and dysmorphic craniofacial features. SRS is caused by DNA hypomethylation at the H19/IGF2-imprinting control region (ICR1) on chromosome 11p15 or maternal uniparental disomy of chromosome 7 (mUPD7) in approximately 50% and 10%, respectivel...

hrp0082fc12.4 | Obesity | ESPE2014

Pediatric Reference Values for Insulin from oGTT and Prevalence of Hyperinsulinemia in Obese Children

Korner Antje , Scheuermann Kathrin , Neef Madlen , Sergeyev Elena , Vogel Mandy , Kratzsch Jurgen , Kiess Wieland

Background: Evaluation of glucose metabolism is currently based on 2 h glucose during an oral glucose tolerance test (oGTT) or fasting glucose and insulin or A1c, as these are the only parameters where cutoff values exist. This does, however, not adequately reflect the degree of hyperinsulinemia due to insulin resistance in obese children.Objective and design: From frequent glucose and insulin levels during an oGTT of 64 healthy lean children (aged 7.7&#...

hrp0082lbp-d3-1007 | (1) | ESPE2014

Hepatic NAD Metabolism is Dysregulated by an Excessive Supply of Lipids

Kiess Wieland , Penke Melanie , Treebak Jonas T , Schuster Susanne , Gorski Theresa , Garten Antje

Background: Animal and human studies have shown that nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme of mammalian NAD biosynthesis from nicotinamide, is modified in non-alcoholic fatty liver disease. Here, we investigated the effect of a high fat diet on hepatic NAD metabolism in mice.Objective and hypotheses: A dysregulation of NAD metabolism is a pathogenic factor for the development of steatohepatitis (NASH).Metho...