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From bedside to bench - Translational medicine and applied research
Overweight and Obesity
Overweight and obesity as well as associated diseases like non-alcoholic fatty liver, insulin resistance and type-2 diabetes have reached epidemic dimensions, with even increasing rates to be anticipated. In our lab, we study different aspects of weight gain and reduction as well as associated complications.
Together with the clinical department of endocrinology we investigate effects of body weight regulation focused on cellular metabolic networks and the development of metabolic diseases. Using RNA-sequencing data from different clinical studies, we aim to elucidate regulatory networks and predictive markers for energy balance in human adipose and skeletal muscle tissue. Based on the RNA-seq data we developed a pipeline to identify possible new targets.
In more detail, relevant molecular mechanisms and their potential contribution in muscle, fat and liver tissues are investigated on the cellular level. Using genetic engineering techniques in cell culture models we can examine the role of target genes and substrates.
Furthermore, we employ Caenorhabditis elegans as model organisms to study genes and their potential function in metabolism, obesity and longevity by RNAi, stress assays, histochemistry and various mutant strains.
For metabolic phenotyping of mouse models we established amongst various other methods the hyperinsulinemic, euglycemic clamp technique, the gold standard assessing insulin action, whole-body glucose uptake and organ specific glucose rates. Beside metabolic characterization of genetic mouse models we are also able to use this technique to investigate the action of pharmacological substances such as new insulins or inhibitors in vivo.
One new aspect of metabolic research in our lab is the study of metabolic consequences linked to the trillions of microbes that live in our gut, usually referred to as the gut microbiota. Specifically, we investigate the causal role of the microbiota in energy balance regulation upon transplantation into a germ-free mouse model. Clinical weight loss studies serve as ideal human interventions to investigate the plasticity of microbial communities under various energy balance states. Finding the best microbial candidates for a beneficial energy balance shift and applying this knowledge into designing novel randomized human weight loss trials using defined bacterial mock communities for supplementation is our primary research goal.
Another approach is the investigation of deep brain stimulation (DBS) in mice as a novel experimental and potential therapeutic approach in the treatment of obesity. Finding new strategies is mandatory since therapeutic opportunities are scarce and a considerable number of patients do not maintain weight loss after lifestyle interventions or even bariatric surgery. Therefore, we aim to investigate this interventional technique targeting the link between the activity of food related brain areas and peripheral hormones to modulate food consumption and metabolic regulation in animal models of obesity.
Please contact us if you have questions related to our research. Our lab is always interested in fruitful collaborations. Potential requests should be addressed to Joachim.Spranger@charite.de (general and clinical issues) and Sebastian.Brachs@charite.de (mouse).