Obesity and dietary fat influence dopamine neurotransmission: exploring the convergence of metabolic state, physiological stress, and inflammation on dopaminergic control of food intake

The aim of this review is to explore how metabolic changes induced by diets high in saturated fat (HFD) affect nucleus accumbens (NAc) dopamine neurotransmission and food intake, and to explore how stress and inflammation influence this process. Recent evidence linked diet-induced obesity and HFD with reduced dopamine release and reuptake. Altered dopamine neurotransmission could disrupt satiety circuits between NAc dopamine terminals and projections to the hypothalamus. The NAc directs learning and motivated behaviours based on homeostatic needs and psychological states. Therefore, impaired dopaminergic responses to palatable food could contribute to weight gain by disrupting responses to food cues or stress, which impacts type and quantity of food consumed. Specifically, saturated fat promotes neuronal resistance to anorectic hormones and activation of immune cells that release proinflammatory cytokines. Insulin has been shown to regulate dopamine neurotransmission by enhancing satiety, but less is known about effects of diet-induced stress. Therefore, changes to dopamine signalling due to HFD warrant further examination to characterise crosstalk of cytokines with endocrine and neurotransmitter signals. A HFD promotes a proinflammatory environment that may disrupt neuronal endocrine function and dopamine signalling that could be exacerbated by the hypothalamic-pituitary-adrenal and kappa-opioid receptor stress systems. Together, these adaptive changes may dysregulate eating by changing NAc dopamine during hedonic versus homeostatic food intake. This could drive palatable food cravings during energy restriction and hinder weight loss. Understanding links between HFD and dopamine neurotransmission will inform treatment strategies for diet-induced obesity and identify molecular candidates for targeted therapeutics.

Automated summary

This review explores the impact of diets high in saturated fat on nucleus accumbens dopamine neurotransmission and food intake, as well as the influence of stress and inflammation on this process. Evidence suggests that high-fat diets can reduce dopamine release and reuptake, disrupting satiety circuits and potentially leading to weight gain. Further research is needed on the interactions between cytokines, endocrine signals, and neurotransmitter signaling in response to high-fat diets to better understand the mechanisms underlying diet-induced obesity and potential targeted therapeutics.