Clash of Titans: AMPK Challenges O-GlcNAcylation in the Failing Heart
Cardiac hypertrophy is a compensatory mechanism that allows the heart to maintain cardiac output under pressure overload. However, sustained pressure overload such as caused by hypertension or aortic stenosis eventually leads to maladaptive cardiac remodelling and ultimately to heart failure. Our lab has previously shown that activation of the AMP-activated protein kinase (AMPK) prevents cardiac hypertrophy by decreasing O-GlcNAcylation, a post-translational modification of proteins that is increased during cardiac hypertrophy and heart failure. The AMPK-mediated inhibition of protein O-GlcNAcylation is due to the direct phosphorylation and inhibition of the Glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate limiting step of the hexosamine biosynthesis pathway, the glucose-related metabolic pathway responsible for the formation of the O-GlcNAc moiety. By using different types of AMPK activators and genetic model of AMPK-deficient mice, we are currently investigating the capacity of chronic AMPK activation to reverse cardiac hypertrophy development when already installed and to prevent heart failure evolution. We are also identifying the O-GlcNAcylated candidate(s) responsible for the development of heart failure with the goal to find innovative therapeutic approach.

SPEAKER BIOGRAPHY

After a Ph.D. in Biological Sciences at the University of Namur in 1997, a 6 years-postdoc at the de Duve Institute of University of Louvain and an internship in the MRC Phosphorylation Unit of Prof. Dario Alessi and Sir Philipp Cohen at the University of Dundee, Luc Bertrand obtained a permanent position at the Belgian National Fund for Scientific Research (FNRS) in 2003 and established his research group in the Institute of Experimental and Clinical Research of UCLouvain. Among others, he was promoted FNRS Research Director in 2019 and Full Professor in 2020, becoming Deputy Dean of the Faculty of Pharmacy and Biomedical Sciences in 2022.
The main scientific interest of Luc Bertrand is the investigation of the intracellular signalling events involved in the regulation of heart metabolism and function during pathophysiological conditions including myocardial infarction and heart failure. A particular focus of his research concerns post-translational modifications (PTMs), not limited to phosphorylation but also to O-GlcNAcylation and acetylation. He is the author of 135 publications with a H-index of 61 for 12.784 citations. He published in major journals of the field including Nature Communications, Cardiovascular Research, Science Translational Medicine, Journal of Molecular and Cellular Cardiology, American Journal of Physiology Heart & Circular Physiology, Cell Metabolism and Circulation.
His scientific career has been marked out by several discoveries revealing the importance of metabolism in the physiological maintenance of cardiac function and the critical deleterious effect of metabolism dysregulation in the onset and progression of major cardiac diseases. Of recent interest, he showed that altered glucose and lipid metabolism occurs rapidly in several cardiac pathologies correlating with a modification of O-GlcNAcylation and acetylation profiles, identifying putative future therapeutic targets to treat heart failure.
Luc Bertrand obtained more than 35 research grants, including the prestigious Belgian WELBIO advanced grant in 2019. I was awarded 5 times including the Lambertine-Lacroix FNRS Prize and the Dr. Léon Dumont Prize of the Belgian Heart & King Baudouin Foundation in 2020.
He is actively engaged in several international scientific organizations. We can cite: Council Member of the European Section of the International Society for Heart Research and President-Elect of the Working Group “Myocardial Function” of the European Society of Cardiology. Accordingly, he was involved in the organisation of numerus international scientific meetings. He is also Consulting Editor of the American Journal of Physiology: Heart and Circulatory Physiology.
During his career, Luc Bertrand performed clean and fair research based on strong evidence, honesty, integrity, and co-operation. He likes to spread such influence on young scientists.
Date: 25 October 2024, 13:00 (Friday, 2nd week, Michaelmas 2024)
Venue: Sherrington Library, off Parks Road OX1 3PT
Venue Details: Sherrington Building
Speaker: Professor Luc Bertrand (University of Louvain)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organisers: Dr Mootaz Salman (DPAG, University of Oxford), Associate Professor Samira Lakhal-Littleton (DPAG, University of Oxford)
Organiser contact email address: events@dpag.ox.ac.uk
Host: Associate Professor Lisa Heather (DPAG, University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Hannah Simm