The effect of dietary fat on dopamine neurotransmission

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Cherie N. Barnes (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Steven Fordahl

Abstract: Emerging evidence has revealed that obesity and diets high in saturated fat are linked with pathophysiological changes in the dopaminergic reward system that disrupt satiety signals governing homeostatic food intake. Diets high in saturated fat are also implicated in the development of a metabolic syndrome-like phenotype characterized by obesogenic weight gain, insulin resistance, and chronic inflammation. While there is evidence that anti-inflammatory unsaturated fats promote healthier metabolic profiles and brain health, little is known about the effects of diets high in unsaturated fat on dopamine neurotransmission which plays a role in feeding and satiety circuits. We sought to determine whether a diet high in unsaturated fat, in contrast to saturated fat, would prevent the development of a metabolic disorders and preserve normal dopamine function. To examine this, male C57BL/6 mice were fed, ad libitum, a low-fat (LF) control diet or a nutrient-matched diet high in either saturated fat (SFD) or unsaturated flaxseed oil (FSO) for six weeks. We measured food intake and body weight throughout the dietary intervention and after six weeks we assessed metabolic dysfunction with glucose tolerance tests and locomotor behaviors in an open field test. We subsequently measured sub-second dopamine release and uptake from dopamine neurons using ex-vivo Fast Scan Cyclic Voltammetry in the nucleus accumbens (NAc). Dopamine kinetics in response to the dopamine D2/D3 receptor agonist quinpirole was also measured to assess dopamine receptor function. In order to assess the relationship between dietary fat, inflammation, and dopamine neurotransmission, the pro-inflammatory cytokine, interleukin-6 (IL-6) was also measured in the NAc. Mice fed a SFD consumed significantly more food and gained significantly more weight compared to their LF-fed counterparts. In addition, unlike the LF group, the SFD group displayed anxiogenic locomotor behaviors in open field tests. Interestingly, the FSO group consumed the same amount of food as the SFD group; however, the FSO diet attenuated weight gain and preserved normal blood glucose regulation and locomotor behaviors. Significantly, the SFD group also exhibited dampened phasic dopamine release, impaired dopamine uptake and increased sensitivity to quinpirole, all of which was prevented with the FSO diet. There was also a negative association between dopamine uptake and IL-6 in the SFD group suggesting IL-6 selectively corresponded with reduced dopamine uptake in mice fed saturated versus unsaturated fat. Collectively, we demonstrate that different types of dietary fat have substantially different effects on metabolic phenotype and dopamine terminal regulation. In contrast to a diet high in saturated fat, a diet high in unsaturated fat preserved both normal metabolic and behavioral parameters as well as dopamine signaling in the NAc.

Additional Information

Language: English
Date: 2019
Dopamine, Fast scan cyclic voltammetry, IL-6, Nucleus accumbens, Saturated fat, Unsaturated fat
Fat $x Physiological effect
Dopamine $x Physiological effect
Dopaminergic mechanisms
Neural transmission

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