ESPE Abstracts

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 ...

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...

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...

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 ...

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 ...

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...

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&#...

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...

Background: Patients with PTEN (phosphatase and tensin homolog) hamartoma tumor syndrome and germ line mutations in PTEN frequently develop lipomatosis, for which there is no standard treatment. Rapamycin was shown to reduce the growth of lipoma cells with heterozygous PTEN deficiency in vitro, but concomitantly induced an up regulation of AKT phosphorylation.Objective and hypotheses: Since it was shown that resveratrol stabilizes PTEN,...

Background: Childhood obesity is a global health problem and co-morbidities develop already during childhood and adolescence. Male obesity impacts negatively on reproductive function. Testosterone is decreased, sperm quality reduced, and the physical and molecular structure of germ cells altered in obese males. However, less is known about the role of prepubertal obesity on future reproductive function. We therefore explored Leydig cell function and reproductive potential in a...