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Partners: Joachim Spranger (Endocrinology, Charité), Jürgen Scholze (Outpatient Clinic, Charité), Philipp Stawowy (Cardiology, DHZB), Simone Spuler (ECRC, Charité), M. Boschmann (ECRC, Charité)
Deregulation of body weight control occurs in two opposite directions: progressive gain of weight which leads to obesity or progressive loss of weight resulting in cachexia. Between these two extremes an interfacial area exists with common molecular mediators of pathogenesis. Based on these joint pathologies, the present research focus metabolism concentrates on molecular mechanisms involved in body weight regulation in a bidirectional manner. Moreover studies of genetic factors and epigenetic DNA modifications shed light on their contribution to metabolic control.
An underlying hypothesis of our work is that all forms of cachexia as seen in COPD, cancer, infections and old age lead to pathophysiologically relevant cardiovascular alterations, namely chronic heart failure, which is clinically relevant for prognosis. Disturbance of the endothelial function and the regulation of peripheral perfusion result in ischemia and hypoxia of the peripheral tissue as well as the induction of reactive oxygen species and inflammation. We have some evidence that all forms of cachexia, independently of their underlying chronic disease, show neurohumoral activation, which is commonly associated with chronic heart failure. Furthermore, cachectic patients almost with no exception are short of breath, fatigue easily and very often show edema, all of which are hallmarks of chronic heart failure. We have shown that several therapies of chronic heart failure display anti-cachectic properties, e.g. ACE inhibitors and beta-blockers. Hence, we are testing whether these cardiovascular therapies are effective in other therapeutical areas than cardiac cachexia. Currently, several projects are focused on cardiovascular drugs and novel compounds on survival, heart function and body composition in a rat model of cancer cachexia.
Obesity is a major risk factor for cardiovascular disease (CVD). Our work is focussing on mechanisms involved in obesity-mediated CVD. Hereby we are concentrating on tissue cross-talk between metabolic tissues such as adipose tissue, skeletal muscle and liver and CV-organs such as the heart and the vasculature. Regulation of tissue crosstalk by endocrine mediators such as nuclear hormone receptors is one of the main topics. We follow a strict translational research approach from cell culture to animal to proof-of-concept studies in humans.
The Research Focus Metabolism is in close collaboration with a series of other clinical and basic research groups. The schematic presentation below shows currently funded collaboration projects at the Charité.