PR002637 (Project)

Description:Non-alcoholic steatohepatitis (NASH) is a rapidly expanding form of liver disease associated with increased risk of cardiometabolic pathologies. Several clinical trials have shown that dietary ω3 polyunsaturated fatty acid (PUFA) supplementation, in particular eicosapentaenoic acid (EPA, 20:5,ω3) and docosahexaenoic acid (DHA, 22:6,ω3), improves health outcomes in NASH patients and lowers cardiovascular diseases. It is shown that ω3 PUFAs can suppress hepatic lipogenesis, resolve hepatic inflammation, and lower plasma triglycerides by reducing the production of hepatic very low-density lipoprotein. In parallel, there is emerging evidence that the gut microbiome can powerfully impact NASH via similar mechanisms. Although dietary PUFA supplementation can strongly impact host lipid metabolic pathways in the liver, it is often overlooked that gut microbiota can also synthesize and degrade diverse lipids. Here, we hypothesized that the ability of dietary PUFAs to suppress NASH and cardiometabolic diseases is dependent on microbe-host co-metabolism of lipids. This study provides a comprehensive lipidomic analysis defining unique dietary fatty acid-microbe-host interactions and have uncovered new insights into how meta-organismal metabolism impacts liver diseases and metabolic disorders.