Gut microbiota-Liver axis: Effect of aerobic exercise on non-alcoholic fatty liver
PI:Professor Shulin Cheng
Funding:NSF
NO：NSFC31571219
Abstract：
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Given the major functional role of the liver in the maintenance of metabolic homeostasis, discovering the root causes and the underlying mechanisms of the progression of NAFLD is essential for finding the effective prevention and treatment strategies in combating NAFLD. Studies have shown that lifestyle such as physical activity and diet is one of the main contributors for NAFLD. Therefore, using exercise may be the most economical way to combat NAFLD. We have previously found that gut microbiota composition in humans is associated with liver fat accumulation and over-expression of several genes related to microbiota-derived inflammation in adipose tissue. Thus, it is possible that NAFLD originates from the gut microbiota. To test our hypothesis that microbiota cause adipose tissue dysfunctionality and increased liver fat content, that exercise could modify the gut microbiota and lipid metabolism in adipose tissue thereby affect liver fat accumulation, this project brings together national and international expertise from different fields of exercise, health and biological science in a multidisciplinary approach to study the role of aerobic exercise through gut-liver axis in NAFLD. The underlying mechanisms will be studied in cultured human adipocytes and animal model and verified by human samples. Particularly, 1) to study whether microbial lipopolysaccharides (LPS) cause inflammation, increased lipid synthesis and insulin resistance in cultured human adipocytes by assessing gene and protein expression from cell cultures using quantitative PCR and Western blot, respectively, and measuring cytokines from culture media by ELISA; 2) to understand which are the underlying molecular mechanisms by studying the role of endogenous cannabinoid receptors using receptor antagonists in cell culture experiments; 3) to further explore whether the molecules secreted from adipocytes increase fat accumulation and insulin resistance in hepatocytes by applying adipocyte culture media to hepatocytes and assessing gene and protein expression by quantitative PCR and Western blot, and finally 4) to verify whether latent or chronic bacterial infections, assessed by a novel high-sensitive method, and LPS are associated with high hepatic fat content in humans. This research project will provide new information about the crosstalk between adipocytes and hepatocytes. If our current hypothesis proves to be true, this will open up the possibility of preventing hepatic fat accumulation and NAFLD by modifying the gut microbiota composition, e.g. through specifically designed exercise interventions, towards a metabolically healthier one.