Thesis Defense Announcement
To: The George Mason University Community
Candidate: Peter Masschelin
Program: M.S. in Biology
Date: Thursday May 11, 2017
Time: 3:00 PM
Place: Krasnow Institute, room 229
George Mason University
Title: “The Effect of the Treatment with Various Lipid Species on Mitochondrial and Cellular Functions of Hepatocytes”
Committee Chair: Dr. Ancha Baranova
Committee Members: Dr. Karl Fryxell, Dr. Aybike Birerdinc
All are invited to attend the defense.
Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic characterized by increased intrahepatic lipid accumulation. In some individuals, NAFLD progresses to non-alcoholic steatohepatitis (NASH), with complications including hepatocellular carcinoma and cirrhosis. As a rise in NAFLD cases has been associated with an increase in the consumption of high levels of fats and carbohydrates (Western Diet) and in obesity, understanding how dietary fatty acids contribute to the development of NAFLD through their effects on mitochondrial fatty acid oxidation and biogenesis may expand an array of potential therapeutics for the treatment of NAFLD. In this study, hepatocytes were treated with two concentrations (800uM and 250uM) of dietary fatty acids (oleic, palmitic, and butyric). These treatments resulted in changes in three factors: lipid accumulation, the ratio of mitochondrial to nuclear DNA, and the levels of gene expression involved in mitochondrial homeostasis and lipid processing. Interestingly, exposure to oleic acid or palmitic acid, although both long-chain fatty acids, did not have the same effect on those three factors. Exposure to a short chain fatty acid (butyric) resulted in lipid accumulation, a differential gene expression pattern involved in beta-oxidation, and no change in the ratio of mitochondrial to nuclear DNA. Overall, this study profiled the dynamic and complex responses of hepatocytes to exogenous free fatty acids. Differences in expression levels of genes involved in beta-oxidation brings some insight into a dynamic interplay of fatty acids, their breakdown by beta-oxidation, and transcriptional regulation in human hepatocytes in response to fatty acids.