Limna - Lausanne Integrative Metabolism Nutrition Alliance


Friday 27th January 2017
10h00 -11h00 - Department of Physiology - Bugnon 7, 1005 Lausanne - Seminar room, 6th floor

The metabolic effects of manipulating the Keap1/Nrf2 antioxidant response pathway during high-fat diet-induced obesity: signaling crosstalk and beyond



Department of Pharmacology & Chemical Biology, University of Pittsburgh, PA, USA.

Nuclear erythroid factor 2 like 2 (Nrf2) is a transcription factor that regulates the adaptive response to exogenous and endogenous oxidative and electrophilic stresses. Kelch-like ECH-associated protein 1 (Keap1) binds Nrf2 in the cytoplasm and facilitates its proteasomal degradation. Electrophilic and oxidative stressors as well as chemical inducers (triterpenoids, dithiolethiones, isothiocyanates) can modify reactive cysteines in Keap1, cause dissociation of Nrf2 from the Keap1/Nrf2 complex, and rescue Nrf2 from proteasomal degradation. Initially it was suggested that the Keap1/Nrf2 pathway is activated during obesity secondary to increased oxidative stress. However, there is increasing evidence of Nrf2 crosstalk with other molecular pathways (e.g. PPARγ, FGF21, Notch), indicating that the role of Nrf2 is not be limited to antioxidant and cytoprotective effects. Using mouse genetic models of gain or loss of Nrf2 function we have investigated the role of Nrf2 in the development of diet-induced obesity and type 2 diabetes with a special focus on liver and adipose tissue. The use of pharmacological Nrf2 pathway activators in clinical trials, such as CDDO-Me (triterpenoid) and sulforaphane (isothiocyanate) in the form of broccoli sprout extract, holds promise for a potential translational impact of the basic research on Nrf2 in obesity.


Dionysios Chartoumpekis has received his medical and then his PhD degree in Endocrinology from the University of Patras, Greece. He is currently a Marie Curie Fellow and Visiting Scholar in the Department of Pharmacology & Chemical Biology at the School of Medicine in the University of Pittsburgh, USA. His research interests include the integration of antioxidant pathways in metabolic signaling with a special focus on the Keap1/Nrf2 system in the setting of obesity and type 2 diabetes. He is currently supported by the European Commission through a Marie Curie International Outgoing Fellowship ( and has received several presentation awards in scientific conferences.

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