The influence of sex and strain on neurobiological and behavioral changes due to diet-induced obesity

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Melissa Sardina Totten (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Keith Erikson

Abstract: Diet-induced obesity (DIO) is linked to several adverse neurobiological and behavioral changes, including altered trace element homeostasis, dysregulated dopamine biology, increased anxiety, and reduced physical activity. These DIO-associated harmful effects on the brain can be influenced by sex and strain. The studies presented in this dissertation address both main effects and interactions between diet, sex, and strain on the obesity-induced dysregulation of iron, manganese, copper, and zinc status in the brain, dopamine release and clearance, behavior related to physical activity, anxiety, motivation, and memory, and mRNA expression of genes related to trace element homeostasis, behavior, and neurodegenerative disease. Male and female C57BL/6J (B6J) and DBA/2J (D2J) mice were fed either a low fat diet (LFD) with 10% kcal from fat or a high fat diet (HFD) with 60% kcal from fat for 16 weeks. Our studies revealed a heterogeneous effect of DIO on many of the neurobiological variables that we evaluated. For example, in the striatum, iron was significantly elevated in B6J female mice but not male mice due to DIO. Similarly, in the hippocampus, zinc was increased in D2J males but deceased in D2J females. There was also a dramatic induction of divalent metal transporter 1, alpha synuclein, and amyloid precursor protein in this brain region due to DIO, but only in the B6J males. Behavior assessments demonstrated that B6J male mice fed a HFD were impacted the most through their display of significantly reduced locomotion, reduced rate of habituation, lack of motivation, and elevated anxiety levels. Interestingly, these mice also showed a significant upregulation of dopamine receptor D2. Dopamine clearance in the dorsal striatum was significantly reduced in both male and female D2J mice due to DIO, while in the nucleus accumbens core, reductions in dopamine clearance occurred for male mice of both strains fed HFD. Collectively, these data provide evidence for important sex and strain differences on the impact of DIO-associated behavior alterations and neurobiology dysregulation. As the incidence of obesity continues to rise worldwide, these findings have key health implications related to debilitating behavior disorders and the development of neurodegenerative disease that can be triggered by an energy dense diet and a state of DIO.

Additional Information

Language: English
Date: 2020
Behavior, Brain, Diet, Dopamine, Elements, Obesity

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