Date of Award


Document Type

Open Access Honors Thesis

Degree Name

Bachelor of Science (BS)




Jill Macoska


Rajini Srikanth

Subject Categories



Metabolic syndrome is often defined by the presence of several factors, including accumulation of abdominal fat, high blood pressure and high blood glucose levels, that increases the risk of developing heart disease, diabetes and cancer. The development of metabolic syndrome has been shown to be very closely linked to lack of physical activity and is increasing concurrent with the rise of obesity rates among adults. Development of metabolic syndrome can have detrimental physiological effects throughout the body and can lead to the development of Non-Alcoholic Fatty Liver Disease (NAFLD). Proper liver function is crucial for the health of the body since it is the site of essential processes such as protein production, blood clotting, metabolism of cholesterol, glucose and iron. Metabolic syndrome contributing to NAFLD can lead to liver dysfunction, hepatitis, cirrhosis, and hepatocellular carcinoma. In this study we used liver RNA from our diet-induce obesity mouse model (mice fed with a 60% fat diet) to characterize the transcriptional landscape of NAFLD and compare it to the transcriptional signature of healthy control mice (mice fed with a 10% fat diet). Understanding the transcriptional differences between these two groups can aid in the understanding of NAFLD and consequent liver pathobiologies. More importantly, the transcriptional signatures identified could also help early detection of these diseases through the identification of novel markers. In this study, we observed significant down-regulation of genes associated with metabolic processes, and significant up-regulation of genes involved in immune responses. Additionally, we also identified up-regulated transcripts in our obese mice reported to be involved in hepatocellular carcinoma and fibrosis. However, the NAFLD livers did not demonstrate histological evidence of carcinoma and/or fibrosis. Therefore, the NAFLD livers already expressed a premalignant signature in the absence of any other indication of cancer. In conclusion, the identification of genes downregulated in metabolic processes and up-regulated in immune responses indicate that our model is indeed exhibiting liver disease. Moreover, the finding of a premalignant signature suggests that NAFLD may begin to progress towards hepatocellular carcinoma much earlier than previously thought.

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