Our research topic
The prevalence of Western diet-induced Metabolic Syndrome (MetS) is booming, contributing to a persistent increase in cardiovascular diseases (CVD), including myocardial infarction, which is the main complication of atherosclerosis development. Thus, understanding the pathogenesis of these co-morbidities and identifying new therapeutic targets is of utmost importance. Many patients with obesity suffer from adverse metabolic complications and associated atherosclerosis, whereas others remain ‘metabolically healthy obese’ (MHO). The discrepancy regarding individual susceptibility to develop CVD is still an issue that is currently not sufficiently addressed. This susceptibility to cardiometabolic diseases is mainly associated with environmental factors such as diet.
We are interested in understanding the links between the diet and cardiometabolic complications: Metabolic Syndrome (MetS) and atherosclerosis.
In particular, we focus on Tryptophan (Trp) metabolism and particularly on one major enzyme involved in Trp catabolism: indoleamine 2,3-dioxygenase 1 (IDO) in the context of cardiometabolic diseases including MetS, atherosclerosis, aneurysm and myocardial infarction.
Our study published in Nature Medicine highlighted the role of Trp metabolism in MetS through IDO activity (Laurans et al. Nature Medicine 2018). We also showed its involvement in aneurysm pathogenesis (Metghalchi et al. Plos one 2018). Moreover, we reported in Cell Metabolism a critical role of IDO activity in the fine tuning of immune responses under high cholesterol diet, with major consequences on atherosclerosis (Metghalchi et al. Cell Metabolism 2015) and myocardial infarction (Melhem et al. Circulation 2021).
We will continue to investigate Trp metabolism role, particularly withinin the gut and how it impacts cardiometabolic diseases by combining mouse models developing MetS and atherosclerosis.