Biological Systems Engineering, Department of


First Advisor

Hyun-Seob Song

Second Advisor

Jaekwon Lee

Date of this Version

Spring 3-2023

Document Type



Naeun Lee, (2023), Metabolic Network Modeling to Unravel the Impact of Copper Deficiency and High-fat Diet on Liver Metabolism. M.S. Thesis, University of Nebraska-Lincoln.


A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Agricultural & Biological Systems Engineering, Under the Supervision of Professors Hyun-Seob Song and Jaekwon Lee.

Copyright © 2023 Naeun Lee


Fatty liver disease is a common health problem caused by an imbalance in the intake, utilization, and distribution of energy. High-fat and high-carbohydrate diets have been identified as major risk factors for fatty liver disease. Other contributors and modifiers can also influence the development of liver damage. Intriguingly, inappropriate copper (Cu) levels in the diet and organs are associated with fatty liver disease, though the exact way in which Cu deficiency or toxicity contributes to metabolic issues is not yet clear. Cu is necessary for several biological processes, including energy production and redox balance. Further research should be taken to determine exactly how Cu deficiency and toxicity cause metabolic complications. To fill in this knowledge gap, this research aimed to use human genome-scale metabolic modeling with incorporating transcriptomic data and determine how Cu deficiency and high-fat diet affect metabolism in the liver. Results revealed that high-fat diet combining with Cu deficiency induces dramatic effects on fatty acid catabolism, energy metabolism, and NADPH balance, which is consistent with gene expression changes. In addition, the model proposed new findings in reduced ascorbate recycling, oxalate synthesis, and betaine synthesis which can affect other minerals or organs. These results presented Cu limitation-induced exacerbation of fatty liver disease and propose underlying mechanisms.

Advisors: Hyun-Seob Song and Jaekwon Lee