Degree

Doctor of Philosophy (PhD)

Department

Nutrition and Food Sciences

Document Type

Dissertation

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disturbances that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and liver cancer. NAFLD affects individuals that consume the typical Western diet consisting of high levels of fats and carbohydrates. The increase in circulating free fatty acids, palmitate and oleate, or lipopolysaccharides (LPS), induce oxidative stress and pro-inflammatory cytokine production in the liver, which all contribute to NAFLD progression. In this study, we are evaluating the mRNA expression of genes associated with fatty acid oxidation (FAO) and the protein expression of pro-inflammatory cytokines related to NAFLD using the HepG2 human liver hepatocellular carcinoma cells exposed to palmitate/oleate or LPS. The treatment of sodium butyrate (NaB) or sodium propionate (NaP) was used to relieve oxidative stress and inflammation in liver cells. The quantitative real-time polymerase chain reaction (qRT-PCR) results show that NaP or NaB, were able to promote FAO, regulate lipolysis, and reduce reactive oxygen species production by significantly increasing the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1 alpha (CPT1α), fibroblast growth factor 21 (FGF21), and uncoupling protein 2 (UCP2) in HepG2 cells. Together, NaP and NaB may produce synergistic effects by significantly increasing CPT1α, PPARα, and UCP2 mRNA expression in LPS-induced HepG2 cells and by significantly increasing CPT1α and ATGL mRNA expression in palmitate/oleate-induced HepG2 cells. Only NaP treatment may have the ability to reverse hepatic steatosis and increase whole-body energy expenditure by significantly increasing FGF21 mRNA expression in palmitate/oleate-induced HepG2 cells. The ELISA results reveal that only LPS significantly increased Tumor Necrosis Factor alpha (TNF-α) expression in HepG2 cells. At the same time, NaP alone or in combination with NaB significantly decreased TNF-α expression in LPS-induced HepG2 cells. The expression of IL-8 in both models showed no significant differences in all treatments. The Western blot analysis of CPT1α protein expression increased by NaP alone or in combination with NaB in the palmitate/oleate model. In conclusion, this study shows promising results for the use of NaP and NaB as a potential new therapy in NAFLD.

Date

1-21-2020

Committee Chair

Losso, Jack

Available for download on Friday, January 15, 2021

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