Fig. 1.

Effects of dietary fat and obesity on hedonic and homeostatic dopamine circuits: homeostatic, dopamine-motivated feeding and reward learning circuits overlap as insulin and leptin convey body energy status to the hypothalamus (Hypo) and VTA. In response, hypothalamic nuclei send appetitive neuropeptides to the VTA and NAc to influence food intake, and NAc dopamine neurotransmission is directly stimulated by hormonal action in the NAc and VTA. This information is also conveyed via dopamine, GABA and glutamate from the VTA to NAc, and the NAc responds by sending GABA to hypothalamic feeding regions, the VTA as a regulatory feedback circuit, and thalamic, motor and cognitive cortical regions. Effects of long-term HFD or palatable food consumption are highlighted by region. This characterises how diet-induced obesity dysregulates key neurotransmitters, neuropeptides and hormones that regulate food intake to reduce dopamine neurotransmission leading to overeating and further weight gain.

TH, tyrosine hydroxylase; D1R/D2R, dopamine type 1/2 receptors; DAT, dopamine transporter; POMC/CART, pro-opiomelanocortin/cocaine- and amphetamine-regulated transcript; NPY/AGRP, neuropeptide Y/agouti-related peptide.