hrp0086rfc13.1 | Management of Obesity | ESPE2016

Inhibition of Teneurin-2 (TENM2) Leads to Upregulation of UCP1 in Human White Adipocytes

Tews Daniel , Fischer-Posovszky Pamela , Wabitsch Martin

Background: Heat generation in UCP-1 active cells as present in brown adipose tissue contributes to the regulation of energy homeostasis. Brown adipose tissue is known to be present in neonates and infants and has recently also been demonstrated in children and adults. Interestingly, a transition of white adipocytes into a brown phenotype has been documented in vitro in mouse and human cells, yet the underlying mechanisms are still not resolved. Using transcriptome an...

hrp0089p1-p125 | Fat, Metabolism and Obesity P1 | ESPE2018

M2 Macrophage Markers are Enriched in Human Deep Neck Adipose Tissue and Do Not Correlate with UCP1 Expression

Tews Daniel , Haggenmueller Benedikt , Wabitsch Martin , Fischer-Posovszky Pamela

Background: Secretion of catecholamines by adipose tissue M2 macrophages was recently proposed as a molecular mechanism leading to activation of brown adipose tissue and heat generation in mice. However, published data are conflicting and it is not clear whether this pathway might play a role in humans. To shed light on this, we studied macrophage polarization in human white and brown adipose tissue and related it to thermogenic gene expression.Methods: ...

hrp0095p1-64 | Fat, Metabolism and Obesity | ESPE2022

microRNA-27a - a strand specific regulator of adipogenesis and adipocyte function

Roos Julian , Wu Hang , Pula Taner , Tews Daniel , Wabitsch Martin , Debatin Klaus-Michael , Fischer-Posovszky Pamela

MicroRNAs (miRNAs) are small non-coding RNA molecules and play an important role in the post-transcriptional regulation of gene expression and thereby influence important cellular functions. In adipocytes, miRNAs regulate key processes such as differentiation, inflammation, metabolism, and adipokine secretion. Recently, we found that miR-27a is upregulated under proinflammatory conditions in human adipocytes. Thus, our goal was to better understand the function of miR-27a in a...

hrp0089p1-p124 | Fat, Metabolism and Obesity P1 | ESPE2018

Metabolic Phenotype of Human Adipocytes Overexpressing UCP1

Tews Daniel , Pula Taner , Funcke Jan-Bernd , Wabitsch Martin , Fischer-Posovszky Pamela

Background: Functional studies on uncoupling protein 1 (UCP1) are important to identify potential pharmacological targets which interfere with energy metabolism. However, current cell models of human origin are scarce due to limited tissue availability. In this study, we generated human preadipocytes and adipocytes with an overexpression of UCP1 and studied the metabolic function of these cells.Methods: Human Simpson-Golabi-Behmel syndrome (SGBS) cells w...

hrp0097rfc3.6 | Fat, metabolism and obesity 1 | ESPE2023

Glucocorticoid-mediated leptin secretion from human adipocytes is dependent on glucose availability

Tews Daniel , Brandt Stephanie , von Schnurbein Julia , Fischer-Posovszky Pamela , Wabitsch Martin

Background: Leptin is produced by adipocytes and regulates central hunger and satiety sensation. While the central leptin effects are well understood, little is known about the regulation of peripheral leptin production. Clinical data demonstrate that leptin levels are rapidly declining upon fasting, suggesting that leptin secretion is acutely regulated by nutrient availability. Although it has been previously shown that leptin secretion is under control by gl...

hrp0095fc4.4 | Fat, Metabolism and Obesity | ESPE2022

Inhibition of Neuritin 1 induces browning in human white adipocytes and protects from obesity in vivo

Tews Daniel , Roos Julian , Winter Gordon , Beer Ambros , Rasche Volker , Nedivi Elly , Debatin Klaus-Michael , Wabitsch Martin , Fischer-Posovszky Pamela

Recently, we identified Neuritin 1 (NRN1) as preferentially expressed in human white compared to brown adipocyte progenitor cells. In mice, Nrn1 deficiency leads to a reduction in body weight, indicating that it might regulate body weight. In this study, we aim to address the function of NRN1 regarding adipocyte metabolism in vitro and in vivo. We used human SGBS preadipocytes as an in vitro model system. NRN1-deficient cells were generated using len...

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...

hrp0082p1-d1-109 | Fat Metabolism & 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 ...

hrp0097p1-59 | Fat, Metabolism and Obesity | ESPE2023

Diagnostic value of soluble LEPR levels in the serum of patients with disease-causing biallelic LEPR variants

Zorn Stefanie , Tews Daniel , von Schnurbein Julia , Flehmig Bertram , Pridzun Lutz , Wabitsch Martin , Malene IV , Chantana Yay , Khun Leang Chhun , Ban Manet , Tyla Martin , Ngee Lek

Introduction: The soluble leptin receptor (sLR) is the main binding protein of leptin in the serum. It reflects the amount of membrane-bound leptin receptors (LEPR) as the sLR is produced by proteolytic cleavage of the extracellular domain of membrane-bound LEPR. Low sLR but high leptin levels were measured in patients with severe obesity. In patients with monogenic obesity caused by biallelic LEPR variants, sLR levels were found to be either undetect...

hrp0097p1-256 | Fat, Metabolism and Obesity | ESPE2023

Serum leptin concentrations in a pooled cohort of 6.105 children and adolescents: Reference values as a function of dependence on sex, age, pubertal stage and BMI-SDS

Brandt Stephanie , Vogel Mandy , Kratzsch Jürgen , Tews Daniel , Pridzun Lutz , Flehmig Bertram , B Ranke Michael , Körner Antje , Kiess Wieland , F Blum Werner , Wabitsch Martin

Background: Current reference values for leptin in childhood and adolescence are presented separately for girls and boys, and as a function of age without considering the variability of fat mass. This complicates the interpretation of measured serum leptin concentrations since fat mass is the major determinant of circulating leptin concentrations. To fill this gap, we aimed at pooling existing data (age, BMI, sex, tanner stage (TS), serum leptin concentrations...