Date of Graduation

5-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Bottje, Walter G.

Committee Member

Hakkak, Reza

Second Committee Member

Dridi, Sami

Third Committee Member

Kong, Byung-Whi

Fourth Committee Member

Rochell, Samuel J.

Fifth Committee Member

Baum, Jamie I.

Keywords

Fatty liver; Global gene expression; Liver steatosis; Non-alcoholic fatty liver disease; Soy protein isolate; Transcriptomic analysis

Abstract

According to the Centers for Disease Control and Prevention (CDC) the prevalence of obesity in adults in the United States during 2017-2018 was a 42.4%, a high number considering all the risks factors associated with this disorder, such as cardiovascular disease, insulin resistance, diabetes type 2, and fatty liver disease, among others. Fatty liver disease is the accumulation of lipids in the liver that can account for more than 5 to 10% of the liver’s weight. There are two types of fatty liver disease, alcoholic fatty liver disease (AFLD), and non-alcoholic fatty liver disease (NAFLD). AFLD is the detrimental accumulation of lipids in the liver due to sustained alcohol consumption. NAFLD is the aggregation of lipids in the hepatocytes that cannot be explain by alcohol intake. In this study, we analyzed the beneficial impact of consuming a soy-based diet in ameliorating the effects of NAFLD on obese Zucker rats.

We conducted global gene expression analysis on samples extracted from livers of Zucker rats that were fed diets containing either soy protein isolate (SPI) or casein (CAS) during 8 (short-term) and 16 weeks (long-term) (Hakkak et al. 2015). In order to validate the transcriptomics data we run qPCR on some of the most deferentially expressed genes, and found good correlation between both using a cut off value of 1.3 fold and P < 0.005. There were several genes either up- or down-regulated in SPI feeding group that are consistent with the literature. There were also novel findings linking the up regulation of a gene (such as NPTX2) with SPI and NAFLD that were never reported before to our knowledge. In addition, we used Ingenuity Pathway Analysis (IPA) software to help us to interpret the data analysis. We compared the effects of the short-term SPI diet versus long-term on the same diet. The results seem to indicate that the longer the obese rats were on the SPI diet the more beneficial were its effects in two main functions we focused on: inflammatory response predicted by IPA to be inhibited, and lipid metabolism, predicted to be activated in SPI feeding versus the control group.

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