Obesity is increasing rapidly in EU, with about 50% of the population being obese. In addition to cardiovascular disease and type-2 diabetes, non-alcoholic fatty liver disease fatty liver disease (NAFLD) is a major obesity-associated chronic disease. The European Association for the Study of the Liver has estimated that up to 44% of obese people (116 million people) are likely to suffer from NAFLD. Some patients will develop non-alcoholic steatohepatitis (NASH), an advanced disease involving inflammation. Despite the high frequency of NAFLD, comprehensive research on its effects on hepatic biotransformation capacity of endogenous and exogenous compounds is lacking, especially in human subjects.
The project aimed to increase understanding of the emerging liver diseases NAFLD and NASH, particularly by evaluating the expression of transporter proteins in the liver of NAFLD and NASH patients. The information on the transporter expression in the diseases is essential for safe drug therapies and will benefit the development of new chemical entities for chronic metabolic and liver diseases. The project focus on the role of OSTα/β as a bile acid and drug transporter particularly in NAFLD. The hepatic expression of OSTα/β is normally low but dramatically increased in the conditions with elevated bile acid levels in the liver, even more than expression of other bile acid transporters. The scientific aims of the project are: 1) the proteomics of bile acid transporters in NAFLD and NASH liver, 2) regulation and mechanisms of OSTα/β transport, and 3) the role of OSTα/β as a bile acid and drug transporter in the human liver in comparison to other hepatic basolateral transporters.
