FXR and GPBAR1 signaling and statin reverses vascular and liver damage in non-alcoholic fatty liver disease
Description
Non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH) are highly prevalent human disorders closely correlated with obesity, metabolic syndrome and at risk for developing atherosclerotic cardiovascular disease (CVD). It is widely established that the CV component dictates the patient outcomes more frequently and to a greater extent than does the progression of the liver component and it is the most common cause of death for NAFLD patients. So, it is recommended that statins should be added to therapy in patients at increased risk for developing CV complications. Atorvastatin is a hydrophobic statin indicated for the treatment of hypercholesterolemia, combined hyperlipidemia and NAFLD. Furthermore, the co-activation of FXR and GPBAR1, two members of bile acid-activated receptors family, by the dual ligands BAR502, represent new therapeutic option for the pharmacological treatment of hepatic and metabolic disorders.The aim of the study was to compare the effects of BAR502 and atorvastatin in two rodent model of atherosclerosis and NAFLD to evaluate the efficacy of their combination. Aorta trascriptome and microbiota of Apolipoprotein E deficient mice (ApoE−/−) and liver trascriptome of C57BL6 mice fed with HFD-F alone or with BAR502, or Atorvastatin, or their combination were analyzed.