Date of Completion

5-29-2021

Thesis Advisor(s)

Christopher N. Blesso, Spencer Nyholm

Honors Major

Molecular and Cell Biology

Disciplines

Medical Microbiology | Molecular, Genetic, and Biochemical Nutrition

Abstract

While greater abundances of Bacteroidetes are associated with better health outcomes, this phylum is a major producer of serine-dipeptide lipids, which are thought to promote inflammation via Tolllike receptor (TLR) stimulation. Lipid 654 (L-654) is one class of serine-dipeptide lipids that has been isolated from arterial plaques and is thought to contribute to atherogenesis. Recent evidence shows that not only does long-term L-654 exposure attenuate atherosclerosis, it also significantly reduces hepatic lipid levels and markers of inflammation in mice. To better understand the impact on the human liver, L-654 was administered to HepG2 hepatocytes at concentrations of 0.5 μg/mL or 1.0 μg/mL for 24 hours. No significant differences were observed in hepatic gene expression related to inflammatory pathways nor cholesterol metabolism in the short-term at the transcriptional level. This conclusion is supported by data from qRT-PCR and RNA-sequencing experiments. Future investigation may consider the impact of serine dipeptide lipids on liver cells other than primary hepatocytes, such as Kupffer macrophages or hepatic stellate cells, which are implicated in the development of fatty liver disease and cirrhosis.

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