The impact of a high-fat diet on physical activity and dopamine neurochemistry in the striatum is sex and strain dependent in C57BL/6J and DBA/2J mice

ABSTRACT

Background

Obesity has been linked to behavioral and biochemical changes, such as reduced physical activity, dysregulated dopamine metabolism, and gene expression alterations in the brain. The impact of a continuous high-fat diet and resulting state of obesity may vary depending on sex and genetics.

Objective

The aim of this study was to investigate the impact of a high-fat diet on physical activity, gene expression in the striatum, and dopamine neurochemistry using male and female mice from different strains as a model to examine sex and strain influences on dopamine-mediated behavior and neurobiology.

Methods

Male and female mice from the C57BL/6J (B6J) and DBA/2J (D2J) strains were randomly assigned a control low-fat diet with 10% kcal fat or a high-fat diet with 60% kcal fat for 16 weeks. We assessed ambulation and habituation using the open field test; dopamine release and reuptake using ex-vivo fast scan cyclic voltammetry; and striatal mRNA expression of dopamine receptor D2, alpha synuclein, and tyrosine hydroxylase.

Results

Mice fed a high-fat diet exhibited reduced motor activity, but only obese B6J male mice displayed reduced habituation. Dopamine clearance in the dorsal striatum was reduced only in obese D2J mice, while dopamine clearance in the nucleus accumbens core was reduced only in male obese D2J mice. Striatal dopamine receptor D2 gene expression was upregulated exclusively in obese male B6J mice.

Conclusion

Our study provides evidence for important sex and strain influences on the impact of a high-fat diet and obesity-induced behavior alterations and neurobiology dysregulation in the striatum.

KEYWORDS:

• High-fat diet
• obesity
• striatum: dopamine
• physical activity
• sex differences

Acknowledgements

The authors acknowledge Paula Cooney for assistance with tissue collection and Mary Martinez for assistance with animal care. Conceptualization and Study Design, MST, SCF, KME; Data Collection and Analysis, MST, CWW, DMP, MCL, SCF, and KME; Manuscript Preparation, MST, CWW, SCF and KME.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This research was funded by the UNC Greensboro Health and Human Sciences Research Grant and Faculty First Award.

Notes on contributors

Melissa S. Totten

Melissa S. Totten, Ph.D. is a graduate of UNC Greensboro from the Department of Nutrition. She is an Associate Professor of Chemistry and Biochemistry at Salem College in the Department of Chemistry.

Conner W. Wallace

Conner W. Wallace, Ph.D. is a graduate of UNC Greensboro from the Department of Nutrition and is now a Postdoctoral Fellow at Atrium Health Wake Forest Baptist.

Derek M. Pierce

Derek M. Pierce, M.S. is a graduate of UNC Greensboro from the Department of Nutrition.

Steve C. Fordahl

Steve C. Fordahl, Ph.D. is an Assistant Professor at UNC Greensboro in the Department of Nutrition where he examines how diet alters dopamine neurochemistry.

Keith M. Erikson

Keith M. Erikson, Ph.D. is a Professor at UNC Greensboro in the Department of Nutrition where he examines how diet impacts neurobiology.