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Role of Betaine Homocysteine Methyltransferase in Regulating Lipid Metabolism in McArdle RH7777 Cells Open Access


Other title
BHMT, lipid metabolism, NAFLD, liver, hepatocytes
Type of item
Degree grantor
University of Alberta
Author or creator
Ab Aziz, Nusaibah
Supervisor and department
Jacobs, Rene (Agricultural, Food and Nutritional Science)
Examining committee member and department
Lehner, Richard (Pediatrics)
Department of Agricultural, Food, and Nutritional Science
Nutrition and Metabolism
Date accepted
Graduation date
Master of Science
Degree level
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. It is a clinical pathological state characterized by the accumulation of triacylglycerol (TG) in hepatocytes. It can progress to non-alcoholic steatohepatitis (NASH) and in some cases to fibrosis and cirrhosis. Previous studies have demonstrated that increased betaine:homocysteine methyltransferase (BHMT) activity protects the liver from excess TG accumulation. BHMT is highly expressed in liver and is important for the synthesis of methionine, an intermediate of S-adenosylmethionine (SAM). The ability of BHMT to regulate hepatic lipid metabolism has been documented, but the precise mechanism is not completely clear. Here we show that expression of rat BHMT1 or BHMT2 in McArdle RH7777 rat hepatoma cells reduces intracellular TG content. Reduction in TG was associated with downregulation of key genes involved in de novo biosynthesis of TG, increased β-oxidation and possibly altered glucose metabolism. This thesis affirms the important role of BHMT in the regulation of hepatic lipid metabolism and provides potential mechanisms by which BHMT prevents hepatic TG accumulation and to our knowledge, this is the first report to show a potential metabolic role for BHMT2 with respect to lipid metabolism.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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