Figure 1. Obesity-induced cellular and circuit level changes in the orexin system are associated with maladaptive behavioral responses.

Chronic HFF alters glutamatergic inputs to orexin/hypocretin neurons (Ox/Hcrt), thereby increasing overall inhibitory tone and inducing a state of hypoarousal. Altered cellular activity of orexin neurons influences the activity of downstream neural networks in the lateral hypothalamus and hippocampus and decreases reward-seeking and coping behaviors. Chemogenetic activation of orexin neurons reverses changes in network activity and corrects the behavioral consequences of HFF (14). GluR, glutamate receptor; D₁R, dopamine 1 receptor; hM3Dq, chemogenic receptor.