hrp0097p1-66 | Fat, Metabolism and Obesity | ESPE2023

Leptin treatment affects adipose progenitor cells physiology

Jasaszwili Mariami , Fuchs Lasse , Richter Sandy , Kirstein Anna , Kiess Wieland , Le Duc Diana , Garten Antje

Introduction: Leptin, an adipokine secreted mainly by adipose tissue, is a regulator of energy balance acting through central mechanisms on the hypothalamus. However, leptin has many functions regulating e.g., immune system and reproduction. Leptin exerts its biological effects through its receptor, the expression of which has been demonstrated in several tissues. There are several leptin receptor isoforms, but activation of only one of them, the long form, re...

hrp0097p1-56 | Fat, Metabolism and Obesity | ESPE2023

Lipoma slice cultures as a new model to examine the effects of PI3K inhibitors on lipid accumulation

Maria Merz Lea , Kallendrusch Sonja , Winter Karsten , Klöting Nora , Krause Kerstin , Le Duc Diana , Kiess Wieland , Garten Antje

Introduction: PTEN hamartoma tumor syndrome (PHTS) is a rare genetic disorder caused by germline mutations in the tumor suppressor gene Phosphatase and tensin homologue (PTEN), a negative regulator of the phosphoinositide-3 kinase (PI3K)/AKT/ mechanistic target of rapamycin (mTOR) pathway. Children with PHTS frequently develop adipose tissue overgrowth, so called lipomas that can lead to loss of organ function due to displacing lipoma growth. Currently, except...

hrp0095fc4.5 | Fat, Metabolism and Obesity | ESPE2022

Pten knockout in osteoprogenitor cells leads to loss of adipose tissue

Kolbig Florentien , Lorenz Judith , Roth Lisa , Lindhorst Andreas , Thor Doreen , Le Duc Diana , Gericke Martin , Kiess Wieland , Klöting Nora , Krause Kerstin , Garten Antje

Background and Aim: Pediatric patients with germline mutations in the phosphatase and tensin homolog (Pten) gene frequently develop aberrant adipose tissue growth called lipomas. In severe cases, recurrent lipoma formation can have adverse effects on organ function and quality of life. Due to the lack of understanding the basis of lipoma development, no systemic treatment options are available. We therefore aimed to characterize an already described lipoma bea...

hrp0095rfc4.3 | Fat, Metabolism and Obesity | ESPE2022

Phospholipid scramblase 4 regulates adipocyte differentiation via PIP3-mediated AKT activation

A.G. Barth Lisa , Nebe Michèle , Kalwa Hermann , Velluva Akhil , Kehr Stephanie , Kiews Wieland , Le Duc Diana , Garten Antje , S. Kirstein Anna

Background and aim: PTEN hamartoma tumor syndrome (PHTS) is caused by germline mutation in the phosphatase and tensin homolog (PTEN) gene. PTEN is a tumor suppressor gene and antagonist of the growth and survival signalling Phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of Rapamycin (mTOR)- cascade. Patients with PHTS, amongst other symptoms, develop lipomas, for which the underlying mechanism is not completely understood. To investigate the role of PTE...

hrp0089p1-p144 | GH & IGFs P1 | ESPE2018

A New p.(Ile66Serfs*93) IGF2 Variant Is Associated with SRS-like Phenotype

Rockstroh Denise , Pfaffle Heike , Le Duc Diana , Roszler Franziska , Schlensog-Schuster Franziska , Heiker John T , Kratzsch Jurgen , Kiess Wieland , Lemke Johannes , Abou Jamra Rami , Pfaffle Roland

The Silver-Russel syndrome (SRS) is characterized by an intrauterine growth retardation accompanied by postnatal growth deficiency. Affected individuals typically have proportionately short statue, finger deformities as well as typical facial features. About 10% of individuals with SRS have maternal uniparental disomy for chromosome 7 (UPD7) and 35%–50% showed hypomethylation of the parental imprinting center region 1 (ICR1) of chromosome 11p15.5. In the recent past also ...

hrp0094p2-73 | Bone, growth plate and mineral metabolism | ESPE2021

PTEN downregulation in mouse osteoprogenitor cells impacts on bone stability and turnover

Lorenz Judith , Kirstein Anna , Nebe Michѐle , Richter Sandy , Le Duc Diana , Kiess Wieland , Kloting-Bluher Nora , Baschant Ulrike , Garten Antje ,

Background: Signaling through the phosphoinositid-3-kinase (PI3K) pathway modulates bone development and remodeling. We aimed to dissect the role of phosphatase and tensin homolog (Pten), a negative regulator of PI3K signaling, in osteoprogenitor cells.Methods: Femura, tibiae and bone marrow stromal cells (BMSCs) from mice with Cre-inducible Pten knockdown in cells expressing the transcription factor Osterix (Pten cKO) a...

hrp0097rfc8.5 | Fat, metabolism and obesity 2 | ESPE2023

Effects of leptin knockdown on a human preadipocyte model

Fuchs Lasse , Jasaszwili Mariami , Richter Sandy , Kirstein Anna , Engelberger Felipe , Künze Georg , Meiler Jens , Lemke Johannes , Kiess Wieland , Le Duc Diana , Garten Antje

Obesity presents a major worldwide challenge, due to its numerous, severe adverse effects on health. This leads to a necessity to further investigate the mechanisms underlying lipid accumulation. The adipocytokine leptin may contribute to this process. While there already has been thorough research into central leptin action, deepening our understanding of leptin’s effects on whole-body energy homeostasis, relatively little is known about its auto- and paracrine effects....

hrp0098rfc11.6 | Fat, Metabolism and Obesity 2 | ESPE2024

Pten knockout in osteoprogenitor cells leads to loss of adipose tissue

Kolbig Florentien , Lorenz Judith , Roth Lisa , Lindhorst Andreas , Thor Doreen , Le Duc Diana , Gericke Martin , Kiess Wieland , Klöting Nora , Krause Kerstin , Garten Antje

Background and aim: Pediatric patients with germline mutations in phosphatase and tensin homolog (Pten) frequently develop aberrant adipose tissue growth/lipomas. In severe cases this can have adverse effects on organ function and quality of life. Due to the lack of understanding the basis of lipoma development, no systemic treatment options are available. We therefore aimed to characterize an already described lipoma bearing mouse model with conditio...

hrp0097p1-510 | Growth and Syndromes | ESPE2023

Tuberous sclerosis complex 1 (TSC1) deficiency leads to increased proliferation of adipose progenitor cells – case report and in vitro studies

Garten Antje , Hentschel Julia , Richter Sandy , Kiep Henriette , Arelin Maria , Platzer Konrad , Merkenschlager Andreas , Kiess Wieland , Mayer Steffi , Abou Jamra Rami , Le Duc Diana , Gerthe Kerkhof , Anita Hokken-Koelega

Introduction&Aim: Activation of mechanistic target of rapamycin (mTOR) as a major regulator of adipogenesis and lipid accumulation is controlled by upstream regulators hamartin/tuberous sclerosis complex (TSC) 1 and tuberin/TSC2. Hamartin and tuberin form a protein complex that inhibits signal transduction to mTOR. The impact of TSC1 deficiency is not clearly defined in human adipose tissue. We identified a likely pathogenic TSC1 splicing variant in a lipo...

hrp0098rfc6.2 | Fat, Metabolism and Obesity 1 | ESPE2024

Genetic Diagnostic Yield of Obesity

Künzel Robert , Faust Helene , Blüher Matthias , Wenzel Eric , Abou Jamra Rami , Jasaszwili Mariami , Kirstein Anna , Kobelt Albrecht , Körner Antje , Lemke Johannes , Stein Robert , Garten Antje , Le Duc Diana

Background/Objectives: Obesity poses a major public health concern. Although studies estimate that the heritability of BMI lies around 40–50%, the underlying genetics are still poorly understood. In monogenic obesity, solitary genetic variations significantly increase obesity risk. We therefore aim to (1) report the diagnostic yield of monogenic obesity using exome-wide data in a large cohort of over 500 individuals and aim to (2) improve future diagnost...