Figure 3. Mechanisms in the homeostatic and hedonic systems leading to food addiction.

a ∣ Diet-induced disinhibition of vagal and hypothalamic satiety mechanisms. A high fat, low fibre diet reduces the release of satiety hormones (GLP1, PYY, CCK) from enteroendocrine cells (EECs) in the gut by dietary fibre-derived short-chain fatty acids (SCFAs), leads to downregulation of receptors for satiety hormones molecules on vagal afferents innervating the EECs, and to a downregulation of the vagally-mediated satiety signaling to the arcuate nucleus of the hypothalamus (ARC). Hypothalamic receptors mediating the effect of other anorexigenic signals (leptin) reaching the ARC via the systemic circulation are also downregulated, resulting in an unrestrained effect of orexogenic signals (ghrelin, insulin, cortisol). Thus, chronic exposure to a high fat, low fibre diet downregulates the inhibitory mechanisms of homeostatic regulation of ingestive behaviors. b ∣ Diet-induced changes in the extended reward system. According to the dopamine deficiency hypothesis, a reduction of dopaminergic stimulation of neurons in the NAc as a result of reduced dopamine relase from the VTA, and a downregulation of dopamine receptors on NAc neurons, reduces the rewarding effects of ingested foods, and leads to craving and overconsumption of unhealthy food in an attempt to compensate for the reduced dopamine signaling. Chronic stress-induced CRF release and glucocorticoid levels also have an inhibitory effect on dopamine signaling. Up and downward arrows inside boxes illustrate reported up and downregulation of respective mechanisms.