Item Details

title

From bench to bedside: the role of polyunsaturated fatty acids and gene-diet interactions in inflammation and trauma

author

Waits, Charlotte Mae Kent

abstract

The liver is primarily involved in regulating lipid metabolism and adapts quickly to changes in dietary fat intake. The type and amount of fat ingested can regulate hepatic lipid composition, metabolism, inflammation and gene expression. For example, dietary polyunsaturated fatty acids (PUFAs) can modulate inflammation and hepatic pathology. Recent studies have identified several genetic variants impacting fatty acid desaturase (FADS) activity and PUFA content in vivo. Notably, single nucleotide polymorphism (SNP) rs174537 has been associated with increased FADS1 activity, where individuals homozygous with the major allele (i.e. GG) have been shown to be “rapid metabolizers” of dihomo-gamma-linolenic acid (DGLA) into arachidonic acid (ARA). In addition, allele-specific methylation (ASM) has been demonstrated with this SNP and CpG sites located within the FADS2 promoter region, such that individuals with the GG genotype have higher levels of DNA methylation. These findings together with the increased dietary intake of omega-6 PUFAs in the Modern Western Diet (MWD), suggest there may be key gene-PUFA diet interactions which play a critical role not only in hepatic function and lipid metabolism, but also in downstream inflammatory pathways leading to human disease. Currently there are few relevant human liver models. Thus, there is a need to develop a new platform which incorporates human-derived cells for the advancement of studying gene-diet interactions.

subject

3D tissue construct

inflammation

liver

polyunsaturated fatty acids

rs174537

trauma

contributor

Rahbar, Elaheh (committee chair)

Howard, Timothy D (committee member)

Langefeld, Carl D (committee member)

Parks, John S (committee member)

Skardal, Aleksander (committee member)

VandeVord, Pamela J (committee member)

date

2020-01-08T09:35:26Z (accessioned)

2022-01-07T09:30:16Z (available)

2019 (issued)

degree

Biomedical Engineering (discipline)

embargo

2022-01-07 (terms)

identifier

http://hdl.handle.net/10339/95955 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation