2ND INTERNATIONAL RESEARCH MEETING 4 JUNE 2010- HÔTEL DE MARIGNY PARIS

2. Bart Staels Diabetes: from risk factors to cardiovascular complications Université Lille Nord de France; INSERM U1011; Institut Pasteur de Lille; Lille, France The « European Genomics Institute of Diabetes » (EGID) project in Lille

3. Obesity predisposes to diabetes and cardiovascular disease

4. Nutrition Exercise Signal transduction pathways Transcription factors Genes Insulin resistance Inflammation Hyper- tension Lipid disorders

5. Clock Sleep-wake cycles Body temperature Activation of intestinal system Endocrine systems Liver metabolism Renal activity Cardiovascular system (blood pressure, heart beat, …) Example 1: Circadian dysregulation and Metabolic disorders

6. Clock outputs Physiological response / metabolic adaptation Metabolic signals Molecular pathways? (ex.Rev-erb  and ROR  ) Chronopharmacology

8. Normal state NR interactome A Cistrome A Regulon A Example 2: Molecular analysis of gene regulation in cardiometabolic diseases Pathological state Epigenetic events NR interactome B Regulon B Cistrome B

9. Lean PPAR  interactome A Cistrome A Regulon A GO functional classification: 1) Extracellular signalling 2) Carboxylic acid metabolism 3) Oxido-reduction 4) Development 5) Subcellular transport Role of the proteasome in the response visceral WAT responsiveness to PPAR  Lefebvre et al. J.Clin.Invest. 2009 Hypoxia UCHL1, Proteasome Obese PPAR  interactome B Regulon B Cistrome B GO functional classification: 1) Monocarboxylic acid and lipid metabolism 2) Mitochondrion 3) Metabolic processes 4) Glucose and pyruvate metabolism 5) Citrate cycle

12. European Genomics Institute of Diabetes : a model of industrie – academia partnership, towards tomorrow’s treatments Basic Research Clinical Research Translational Research Valorisation Platform Pharmaceutical industrie