The role of neuroendocrine-inflammatory axis in the pathogenesis of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disorders associated with fatty liver in the absence of alcohol abuse or other liver disease. Insulin resistance has a central role in the development of NAFLD. The aim of our project will be to determine the role of neuroendocrine-inflammatory axis in the pathogenesis of NAFLD in C57BL/6 mice fed on high-fat diet with low contents of choline and methionine. Gene and protein expression of neuropeptides, cytokines, gut-derived hormones and adipokines will be determined in the brain, liver, gut mucosa and adipose tissue. The role of adiponectin in NAFLD will be determined by administration of adiponectin in combination with high-fat diet. Endocannabinoid modulation of the neuroendocrine-inflammatory axis will be investigated by application of CB1 receptor antagonists, rimonabant and SR141716A. For determination of the role of galectin-3 in the pathogenesis of NAFLD galectin-3 knockout mice will be used. They will be fed with high-fat or standard diet and their cytokine, adipokine and neuropeptide profiles will be compared with profiles in wild-type mice on the corresponding diet. The understanding of the role of neuroendocrine-inflammatory axis in the pathogenesis of NAFLD should improve the therapy of this disease and should contribute to the more efficient prevention of NAFLD.