OSTtrans · The Role of OSTα/β as a Bile Acid and Drug Transporter in Obesity-Associated Chronic Liver Disease, Nonalcoholic Fatty Liver Disease
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-09-01 → 2021-03-03
- EU contribution
- €179,326
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
The Role of OSTα/β as a Bile Acid and Drug Transporter in Obesity-Associated Chronic Liver Disease, Nonalcoholic Fatty Liver Disease
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.
Data: CORDIS, © European Union
Project objective
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. Despite the high frequency of NAFLD, comprehensive research on its effects on hepatic biotransformation capacity is lacking, especially in human subjects. This project will use human liver tissues, human hepatocytes, organic solute transporter α/β (OSTα/β) over-expressing human cells and membrane vesicles, to evaluate the role of OSTα/β and other bile acid transporters in NAFLD, addressing a key question in current biomedical research: Can obesity lead to altered hepatic biotransformation and modulate the efficacy and safety of medications? The main objective is to elucidate 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 cholestatic conditions, even more than expression of other bile acid transporters. The project will focus on the proteomics of bile acid transporters and bile acid metabolome in NAFLD and NASH liver, regulation and mechanisms of OSTα/β transport, and the role of OSTα/β as a bile acid and drug transporter in the human liver. The project is strongly interdisciplinary, involving a combination of biochemistry, molecular biology, and analytical chemistry. The results will increase the understanding of NAFLD disease mechanisms, thus benefitting clinicians and authorities to ensure safe and effective drug therapies for the NAFLD population. This project examines one of the key priorities of European Commission, chronic diseases. In addition, the Applicant enhances her competences and the host widens its networks, thus supporting mutual knowledge transfer.
Original text from CORDIS.
Participants
- ITA-SUOMEN YLIOPISTO · KUOPIOCoordinatorFinland
Links
Data: CORDIS, © European Union