Role of glucose sensors in hepatic physiology and Metabolic Associated Steatotic Liver Disease (MASLD)

Summary:

Our projects aim at unravelling the molecular and biochemical mechanisms underlying the control of intermediary metabolism by nutrients and hormonal signals under both physiological and pathophysiological conditions including type 2 diabetes (T2D), insulin resistance and metabolic associated steatotic liver disease (MASLD). Our group particularly focuses on the regulation and function of two glucose sensors: OGT (O-GlcNAc transferase) a key enzyme of O-GlcNAcylation, a post-translational modification which depends on nutrient availability, and the glucose-sensitive transcription factor ChREBP (Carbohydrate responsive element binding protein), crucial in cells for glucose-sensing and/or energy homeostasis. We and others recently reported that OGT and O-GlcNAcylation play a central role in cell signaling, metabolic regulations, inflammatory processes and response to various cellular stresses, including oxidative stress and increased reactive oxygen species (ROS) production. We recently developed mouse models with a constitutive and/or inducible deletion OGT in hepatocytes. Our results suggest that OGT exerts a protective role against cell damage and tissue injuries induced by exacerbated inflammatory processes (Ortega, Parlati et al. J HEP Reports2023).The underlying mechanisms are currently being explored.

Biography :

Catherine Postic, a CNRS Director of Research, is team leader, scientific advisor of the Metabol’IC Platform and director of the Metabolism and Endocrinology department at Institut Cochin Inserm U1016 in Paris. Catherine Postic earned her doctorate at the University Paris 7 in Paris. She completed post-doctoral work at Vanderbilt University in Nashville, TN USA, during which she was trained in the field of molecular biology and achieved the making of a conditional locus for the glucokinase (gck) gene, a key gene of glucose metabolism. Her team now focuses on hepatic contribution to energy homeostasis, and particularly aims at understanding the molecular mechanisms involved in metabolic associated steatotic liver disease (MASLD). She has authored >100 publications, is internationally recognized in the field of liver pathophysiology and was awarded the CNRS Silver Medal in 2015.  

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