Uncovering the role of bile acid signaling in facilitating sex differences during hepatocarcinogenesis and liver metabolism
Dean, Angela Elizabeth
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Permalink
https://hdl.handle.net/2142/124508
Description
Title
Uncovering the role of bile acid signaling in facilitating sex differences during hepatocarcinogenesis and liver metabolism
Author(s)
Dean, Angela Elizabeth
Issue Date
2024-04-15
Director of Research (if dissertation) or Advisor (if thesis)
Anakk, Sayeepriyadarshini
Doctoral Committee Chair(s)
Erdman, Jr., John W
Committee Member(s)
Gaskins, H. Rex
Nelson, Erik R
Department of Study
Nutritional Sciences
Discipline
Nutritional Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Bile acids
Farnesoid X Receptor
Small Heterodimer Partner
Estrogen Receptor
Hepatocarcinogenesis
Abstract
Sex differences in liver physiology and metabolism have been known for several decades, and many of these differences are attributed to estrogen, androgen, or growth hormone signaling. Here, we focus on sex differences in bile acids, which are known for fat digestion, and their metabolism is orchestrated between the host and the gut microbiota. Bile acid homeostasis is altered during hepatocellular carcinoma (HCC), and therefore, we will examine if they are sex-specific. Bile acid can also signal through receptors and regulate many metabolic processes in the liver. Chapter 1 covers the background of this dissertation, and how nutrients impact bile acid composition and levels is detailed in Chapter 2. A review of sex differences in multiple nuclear receptors along the digestive tract is addressed in Chapter 3. Using a mouse model of bile acid dysregulation that develops cancer, we examine the interactions between bile acids and microbiota in a sex-dependent manner in Chapter 4. Next, we investigate if bile acids can bind to estrogen receptor α and if this interaction between signaling pathways can mediate amino acid metabolism in Chapter 5. Finally, Chapter 6 demonstrates that the endogenous bile acid receptor, FXR, can mediate ductular reaction and heme biosynthesis. These studies show that bile acid homeostasis is complex and controlled by the host and microbiota. Bile acid signaling also controls multiple facets of sex-dependent liver metabolism in physiology and pathology.
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