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

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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
Waits, Charlotte Mae Kent (author)
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)
2019 (issued)
degree
Biomedical Engineering (discipline)
2022-01-07 (liftdate)
embargo
2022-01-07 (terms)
identifier
http://hdl.handle.net/10339/95955 (uri)
language
en (iso)
publisher
Wake Forest University
title
From bench to bedside: the role of polyunsaturated fatty acids and gene-diet interactions in inflammation and trauma
type
Dissertation

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