Interleukin-6 and tumor necrosis factor-α attenuate dopamine release in mice fed a high-fat diet, but not medium or low-fat diets

ABSTRACT

Chronic low-grade inflammation is associated with a state of diet-induced obesity that impacts systemic tissues and can cross the blood–brain barrier to act directly on the brain. The extent to which pro-inflammatory cytokines released in these conditions affect dopamine presynaptic neurotransmission has not been previously investigated. The purpose of this study was to examine how dopamine terminals are affected by pro-inflammatory cytokines, and to determine if dietary fat consumption potentiates cytokine effects on dopamine release and reuptake rate in the nucleus accumbens (NAc). Male and female C57BL/6J mice were fed high, medium, or low-fat diets (60%, 30%, or 10% total kcals from fat, respectively) for six weeks. Fast scan cyclic voltammetry (FSCV) was used to measure dopamine release and reuptake rate in the NAc core from ex vivo coronal brain slices. Electrically evoked dopamine release and the maximal rate of dopamine reuptake (V_max) were significantly lower in mice fed the 30% and 60% high-fat diets compared to the 10% low-fat group (p < 0.05). IL-6 5 or 10 nM or TNFα 30 or 300 nM was added to artificial cerebrospinal fluid (aCSF) bathed over brain slices during FSCV. No effect on dopamine release or V_max was observed with lower concentrations. However, 10 nM IL-6 and 300 nM TNFα significantly reduced dopamine release in the 60% fat group (p < 0.05). No effect of added cytokine was observed on V_max. Overall, these data provide evidence that dietary fat increases neural responsiveness to cytokines, which may help inform comorbidities between diet-induced obesity and depression or other mood disorders.

KEYWORDS:

• Dopamine
• Inflammation
• Diet-induced Obesity
• Saturated Fat
• Voltammetry
• Neurochemistry
• High Fat Diet
• TNFα
• IL-6

Acknowledgements

SCF conceptualized the study and prepared the study design; HAE, CWW and SCF collected and analyzed data; HAE, CWW and SCF involved in manuscript preparation.

Disclosure statement

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

Additional information

Funding

The present study was supported by the Nutrition Department at the University of North Carolina at Greensboro. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R15DK119897 (SCF) and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number T32AA007565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Notes on contributors

H. A. Emmons

Heather A. Emmons is a Ph.D. student in the Nutrition Department at UNC Greensboro.

C. W. Wallace

Conner W. Wallace is a Postdoctoral Research Fellow at Wake Forest School of Medicine.

S. C. Fordahl

Steve C. Fordahl, Ph.D. is an Assistant Professor at UNC Greensboro