Pharm.D. (six years)
Biomedical and Pharmaceutical Sciences
hepatic steatosis; non-alcoholic fatty liver disease; BDE-47; mice
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Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of fat in liver cells that is not due to alcohol consumption. Steatosis results when more than 5-10% of the liver’s weight consists of fat. People who are overweight, or who have diabetes or high cholesterol are more likely to develop NAFLD. Over time, NAFLD can advance to cause cirrhosis, and eventually, liver cancer or failure.
Polybrominated diphenyl ethers (PBDEs, BDEs) are brominated flame- retardants, and are found in many plastics and household products such as cars, textiles, televisions, and computers. BDEs are released into the environment and can reach humans by being ingested or inhaled. Accumulation of this environmental pollutant has been discovered and studied in the human liver, with implications on the induction of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Previous literature has shown wide distribution of BDEs to the liver, with BDE-47 being the most prominent detected in the liver and tissues, in both mice and humans. The effects of BDE-47 after its administration in mice will be explored to demonstrate the link between its exposure and predicted accumulation in the liver.
Preliminary studies have been conducted to determine the effects of BDE exposure on cultured human hepatocytes (HepG2 cells). The BDE-47-treated HepG2 cells displayed an increase in total lipids and triglycerides, as well as an increase in modulated lipogenic gene expression, suggesting BDE-47 has a potential to induce lipid accumulation in human liver. However, a limitation to HepG2-based studies is the lack of significant extension of the findings in vitro to an in vivo model. We hypothesized that administration of BDE-47 in mice fed either a normal or high fat diet would increase liver fat content. For a period of approximately 8 weeks, adult male mice were fed BDE-47 through their diets (0.0003% in 10% kcal or 45% kcal high fat diets). Food consumption and body weights were collected every 2 to 3 days. Through lipid and triglyceride assays, quantification and analysis of hepatic lipid and triglyceride contents of each mouse were measured as markers of fat accumulation and steatosis. Gene expression will also be tested and measured to determine what genes, in the presence of BDE-47, will stimulate lipogenesis, which can further contribute to fat accumulation. BDE-47 exposure data from this animal study and its implications in hepatic accumulation, steatosis and NAFLD will be presented.