Unravelling the role of AKR1D1 in human hepatocytes
<p>Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is rapidly becoming one of the leading indications for liver transplantation worldwide. The cellular processes and molecular targets that govern disease development and progression remain to...
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| Format: | Thesis |
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2017
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| _version_ | 1797092976714842112 |
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| author | Nikolaou, N |
| author2 | Hodson, L |
| author_facet | Hodson, L Nikolaou, N |
| author_sort | Nikolaou, N |
| collection | OXFORD |
| description | <p>Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is rapidly becoming one of the leading indications for liver transplantation worldwide. The cellular processes and molecular targets that govern disease development and progression remain to be fully defined and currently there are no licensed treatments. Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyses a fundamental step in bile acid synthesis. I have hypothesised that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis.</p> <p>In human hepatoma cell lines, genetic manipulation of AKR1D1 altered primary bile acid biosynthesis and steroid hormone action. Furthermore, gene silencing of AKR1D1 increased hepatocyte triglyceride accumulation through increased de novo lipogenesis and decreased β- oxidation, fueling hepatocyte inflammation as well as increasing glycogen synthesis. I have shown that AKR1D1 has a potent ability to regulate the metabolic phenotype of human hepatocytes suggesting a crucial role in the pathophysiology of NAFLD.</p> |
| first_indexed | 2024-03-07T03:53:43Z |
| format | Thesis |
| id | oxford-uuid:c224fa03-040d-447e-9d25-ab268da26274 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:53:43Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | oxford-uuid:c224fa03-040d-447e-9d25-ab268da262742022-03-27T06:06:47ZUnravelling the role of AKR1D1 in human hepatocytesThesishttp://purl.org/coar/resource_type/c_db06uuid:c224fa03-040d-447e-9d25-ab268da26274ORA Deposit2017Nikolaou, NHodson, LTomlinson, J<p>Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is rapidly becoming one of the leading indications for liver transplantation worldwide. The cellular processes and molecular targets that govern disease development and progression remain to be fully defined and currently there are no licensed treatments. Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyses a fundamental step in bile acid synthesis. I have hypothesised that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis.</p> <p>In human hepatoma cell lines, genetic manipulation of AKR1D1 altered primary bile acid biosynthesis and steroid hormone action. Furthermore, gene silencing of AKR1D1 increased hepatocyte triglyceride accumulation through increased de novo lipogenesis and decreased β- oxidation, fueling hepatocyte inflammation as well as increasing glycogen synthesis. I have shown that AKR1D1 has a potent ability to regulate the metabolic phenotype of human hepatocytes suggesting a crucial role in the pathophysiology of NAFLD.</p> |
| spellingShingle | Nikolaou, N Unravelling the role of AKR1D1 in human hepatocytes |
| title | Unravelling the role of AKR1D1 in human hepatocytes |
| title_full | Unravelling the role of AKR1D1 in human hepatocytes |
| title_fullStr | Unravelling the role of AKR1D1 in human hepatocytes |
| title_full_unstemmed | Unravelling the role of AKR1D1 in human hepatocytes |
| title_short | Unravelling the role of AKR1D1 in human hepatocytes |
| title_sort | unravelling the role of akr1d1 in human hepatocytes |
| work_keys_str_mv | AT nikolaoun unravellingtheroleofakr1d1inhumanhepatocytes |