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INVESTIGATION INTO GENE-BY-DIET INTERACTIONS AND THE ROLE OF THE GUT MICROBIOME IN DIET-INDUCED CHANGES ON METABOLIC AND BEHAVIORAL TRAITS IN HETEROGENEOUS STOCK RATS

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abstract
Obesity and mental health show a bidirectional relationship and each is influenced by genetic background, diet, and the gut microbiome. However, factors arising from these influences which are shared between obesity and mental health are not well-understood. Here, we utilized heterogeneous stock (HS) rats to investigate the roles of genetics, sex, and the gut microbiome in metabolic and behavioral responses to high fat diet (HFD). Male and female rats were fed HFD or low fat diet (LFD) prior to metabolic and behavioral testing. Metabolic outcomes included body weight, visceral fat pad weight, fasting glucose and insulin, and glucose tolerance. Behavioral outcomes included anxiety-like (elevated plus maze – EPM, and open field test – OFT) and passive-coping behaviors (forced swim test – FST). Overall, we found that HFD negatively impacted metabolic health in male and female rats, but only male rats showed worsened behavioral health following HFD. We also found that while metabolic traits were influenced by genetics, there was no interaction between genetic background and diet on metabolic phenotypes. Alternatively, we did find evidence for gene-by-diet interaction in male behavioral responses. Finally, our investigation of the gut microbiome found that genera abundances were associated with metabolic, but not behavioral, phenotypes. In conclusion, we found that HFD worsened metabolic health independent of genetics and that metabolic outcomes were associated with gut microbiome genera abundance. In contrast, the sexually-dimorphic behavioral responses to HFD showed evidence of gene-by-diet interaction in males and no association with gut microbiome genera abundance.
subject
Behavior
Gut microbiome
Heritability
High fat diet
Obesity
Outbred
contributor
Deal, Aaron W. (author)
Solberg Woods, Leah C (committee chair)
Shively, Carol A (committee member)
Langefeld, Carl D (committee member)
McClain, Donald A (committee member)
Yadav, Hariom (committee member)
date
2022-09-17T08:35:44Z (accessioned)
2022 (issued)
degree
Molecular Medicine and Translational Science (discipline)
2023-09-16 (liftdate)
embargo
2023-09-16 (terms)
identifier
http://hdl.handle.net/10339/101255 (uri)
language
en (iso)
publisher
Wake Forest University
title
INVESTIGATION INTO GENE-BY-DIET INTERACTIONS AND THE ROLE OF THE GUT MICROBIOME IN DIET-INDUCED CHANGES ON METABOLIC AND BEHAVIORAL TRAITS IN HETEROGENEOUS STOCK RATS
type
Dissertation

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