Item Details

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

author

Deal, Aaron W.

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

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)

2023-09-16T08:30:06Z (available)

2022 (issued)

degree

Molecular Medicine and Translational Science (discipline)

embargo

2023-09-16 (terms)

identifier

http://hdl.handle.net/10339/101255 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation