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Experimental Research
Paediatric endocrinology and diabetology as a university field of expertise is characterised by a strong experimental research interest. Our current experimental research interests lie in the biology and pathophysiology of human adipose tissue and associated diseases such as lipodystrophy, variants and mutants of leptin, inflammation in adipose tissue and metabolic syndrome/insulin resistance.
Current scientific focus
SGBS cells are mesenchymal stem cells obtained from a patient with Simson-Golabi-Behmel syndrome. These stem cells have the property that they can differentiate into human adipocytes in vitro. The ability to differentiate is stable over many generations. This is the main difference compared to mesenchymal stem cells obtained from healthy volunteers. Due to this stable differentiation capacity over generations, SGBS cells are still the most widely used and recognised in vitro system for studying the biology of human adipocytes. Our laboratory supplies over 200 research laboratories worldwide with this cell strain. Many joint projects have been developed in co-operation with international working groups.
Publications
We specialise in the functional characterisation of known and newly discovered genes that cause lipodystrophies. We use SGBS cells, mesenchymal stem cells, HEK cells and genetically modified mouse models for this purpose.
Publications
In most patients, obesity-promoting living conditions or polygenetic defects (several genes are affected) lead to obesity. Monogenic forms, in which defects (mutations) in a single gene are the cause of obesity, are very rare.
Leptin mutations (leptin deficiency and biologically inactive leptin)
The hormone leptin is produced in adipose tissue and plays an important role in the body, including regulating body weight by reducing food intake and increasing energy expenditure. Certain mutations in the leptin gene can lead to leptin deficiency (hormone is not produced and/or not secreted). People with a genetic defect in leptin experience persistent weight gain and even extreme obesity.
Our research group has identified patients with biologically inactive leptin for the first time. In contrast to leptin deficiency, the hormone is produced and can be detected in the blood in normal or elevated concentrations, but is biologically inactive. The determination of leptin bioactivity can be carried out in our endocrinological laboratory. Our discoveries and scientific work have led to a new classification of leptin deficiency states.
For patients who have a leptin deficiency or biologically inactive leptin, there is the option of leptin replacement therapy using a recombinant human leptin analogue (metreleptin). Our Centre for Rare Endocrine Diseases is one of the few specialised centres worldwide that successfully carries out leptin replacement therapy.
Leptin receptor mutations
Leptin mediates its specific effect in the body by binding to and activating the leptin receptor. If the leptin receptor is altered by mutations, leptin can no longer bind and the effect is lost.
A new therapeutic option for patients with certain leptin receptor mutations using the active substance setmelanotide, a melanocortin 4 receptor (MC4R) agonist, is currently in Phase III clinical trials (see the study sponsor's homepage https://www.rhythmtx.com/). Our section is one of four European trial centres involved in the clinical trial of setmelanotide in patients with a leptin receptor defect. Results to date show that daily administration of setmelanotide leads to a rapid and significant reduction in hunger and body weight.
Further information on the clinical trial with setmelanotide can be found here.
Publications
Hibernators and rodents have brown adipose tissue, which regulates energy metabolism through the process of adaptive non-shivering thermogenesis. In humans, it is present in newborns and has recently been shown to be present in adults. The property of brown adipose tissue - the burning of large amounts of energy - makes it an attractive target organ for the development of therapeutic strategies to combat obesity.
The research group is investigating the regulation of proliferation, differentiation and function of human brown (pre-) adipocytes in vitro. The model systems used are brown preadipocytes obtained from surgical material from subjects of different ages, mesenchymal stem cells isolated from bone marrow, which differentiate into brown adipocytes in vitro, and the human preadipocyte cell line SGBS, in which markers of a brown adipocyte phenotype can be expressed. The use of human model systems to study brown adipose tissue is unique and offers the opportunity to gain new insights into the origin of brown human adipocytes and the regulation of their recruitment and function.
Publications
Topics:
- Regulation of brown adipose tissue development in humans/ brown adipose tissue
- Death receptors in adipose tissue
- MicroRNAs in adipose tissue
- Leptin
Clinical Research
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