Arbeitsgruppen und Forschungs­aktivitäten

Hauptziel unserer Forschung im Bereich Prävention und Therapie von Adipositas und kardiometabolischen Begleiterkrankungen ist ein besseres Verständnis der Auswirkungen von Umweltfaktoren und Lebensstil auf sensorische Mechanismen, über die der menschliche Körper auf Veränderungen der Umgebungsbedingungen reagiert. Unser besonderer Fokus liegt auf Veränderungen des Zusammenspiels zwischen dem Darmmikrobiom, dem angeborenen Immunsystem und deren Interaktion mit dem kardiovaskulären und zentralen Nervensystem sowie der individuellen Risiko-Stratifizierung und Prävention von metabolischen und kardiovaskulären Folgeerkrankungen. 

• Bariatric surgery as a key model to unravel microbiome-basesed treatment targets modulating tissue thermogenesis (TRR 333)
• Targeted modulation of gut microbiota activity shaping the cardiometabolic phenotype in metabolic syndrome: Role of novel metabolite candidate signaling (TRR 333)
• From the gut to the brain: Understanding the functional link between metabolic diseases and neurodegeneration    
• Identification and Validation of Cell-type specific Signaling Pathways recruited by Next Generation Incretin-based Anti-diabesity Drugs 
  Obesity therapy currently experiences the market entry of a plethora of novel anti-obesity drugs (AODs) that could revolutionize disease management strategies. While safety and efficacy of these tailored drugs (long-acting GLP-1 agonists, twincretins etc.) performed quite convincingly in clinical trials, their impact on cell type - specific disease pathways is largely uncharacterized. In particular, the impact of these drugs on immune cells and subsequent regulation of pro-/anti-inflammatory signaling remains unknown. Here we aim to describe the signaling processes initiated by AODs in patient- derived immune cell populations using peripheral blood mononuclear cells (PMBCs), stimulation with AODs or conditioned sera, and phospho-proteome analyses. Mapping of differentially phosphorylated proteins onto signaling networks will identify those functional modules that are affected by specific drug compounds. The results will help to describe drug effects in the context of obesity- associated inflammation.)
• Metabolism of (epicardial) adipose tissue on cardiovascular health (TRR 333)
  Adipocytes have a crucial role in energy homeostasis and metabolism due to their role as most important energy storage in mammals. While white adipocytes store excess energy as fat, so called brown adipocytes are specialized to consume energy and produce heat in a process termed non-shivering thermogenesis, which is essential to keep newborn mammals warm. Importantly, recent findings not only showed that also human adults possess metabolically active brown fat, but that its abundance and activity is positively correlated with cardiovascular health.
  Metabolism of brown adipose tissue is research focus of the novel Collaborative Research Center (CRC) TRR333 Brown and Beige Fat – Organ Crosstalk, Signaling and Energetics (BATenergy). Please see consortium homepage: www.trr333.uni-bonn.de for further information)
• AI-POD: Transforming Obesity-related Risk Prediction with Advanced AI Tools (EU-Project)
  AI-POD is driven by a consortium of eleven partners from eight European countries, with the ambitious goal of reducing cardiovascular disease (CVD) risks in the obese population through innovative AI-based predictive tools. Our interdisciplinary team brings together world-renowned experts in fields ranging from cardiovascular CT imaging and computational imaging to obesity research, ensuring a collaborative effort that promises to revolutionize risk assessment through the integration of artificial intelligence in clinical settings.
  Links: AI-POD – Transforming Obesity-related Risk Prediction with Trustworthy AI / AI-POD-Studie Bergmannsheil
• Targeting the gut microbiota to modulate human obesity and related metabolic diseases – a prospective, double-blinded FMT clinical trial (DFG)
  Based on recent outcome data from our experimental work, this DFG-funded clinical project (in cooperation with University of Graz, Austria) explores the functional impact of post-surgery microbiome alterations on host energy metabolism and glucose homeostasis via Fecal microbiota transfer (FMT) in human subjects. In a double-blinded proof-of-concept study, we here perform autologous versus allogenic FMT from lean and obese volunteers as well as from those after bariatric surgery into obese recipients. Additionally to effects on energy and glucose homeostasis, intervention-specific alterations on the microbiota composition and metabolite signature will be profiled by using multi-omics analyses. The major aim is to explore the scientific rational for targeted gut microbiota modulation in management of obesity and related metabolic diseases)
• A Clinical Trial of Tirzepatide (LY3298176) in Participants With Overweight or Obesity and PCOS-related Ovarian Dysfunction -- PERIODS
  Obesity and metabolic syndrome share key pathological mechanisms with infertility disorders in both women and men. The rising prevalence of premature infertility features a major concern in western countries, affecting now about 10-20% of couples in Germany. While systemic insulin and neuronal leptin resistance are well-known mediators of compromised ovulation in women and attenuated spermatogenesis in men, cause-specific treatment modalities for improving reproductive success are not available.
  PERIODS is a multicentric, prospective, randomized, double-blinded phase IV Trial, which studies the effect of the novel GLP-1/GIP-R co-agonist tirzepatide on ovarian dysfunction and infertility in overweight or pbese women with polycystic ovarian syndrome (PCOS).