Hepatocyte endocannabinoid system and innate immunity influence whole-body lipid metabolism : investigation of the molecular mechanisms in the context of obesity
(2020)
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- Authors
- Supervisors
- Cani, Patrice D.
- Abstract
- Nowadays, the prevalence of obesity-related liver diseases is increasing around the globe. However, the efficacy of the available treatments is still limited suggesting that new therapeutic strategies must be discovered. In this thesis we aimed to understand better the etiology of hepatic disorders by examining the impact of two proteins: the first one belonging to the immune system (MyD88) and the second one to the endocannabinoid system (NAPE-PLD). To reach this goal, we investigated the consequence of their deletion in hepatocytes in two distinct mouse models (Myd88∆Hep and Napepld∆Hep). Surprisingly, we discovered that both mutant mice were prone to liver inflammation and hepatic fat accumulation. Additionally, one crucial bioactive lipid family (i.e. bile acids) that regulates host homeostasis and inflammation was strongly altered in both Myd88∆Hep and Napepld∆Hep mice compared to WT. This thesis thereby provides new insights into the regulation of bile acids by two systems that seemed, at first, unrelated to this lipid family and emphasizes the importance of a proper regulation of molecules involved in their regulation to tackle the emergence of metabolic disorders.
- Affiliations
Citations
Lefort, C. (2020). Hepatocyte endocannabinoid system and innate immunity influence whole-body lipid metabolism : investigation of the molecular mechanisms in the context of obesity. https://hdl.handle.net/2078.5/116716