The anterior insular cortex unilaterally controls feeding in response to aversive visceral stimuli in mice

Reduced food intake is common to many pathological conditions, such as infection and toxin exposure. However, cortical circuits that mediate feeding responses to these threats are less investigated. The anterior insular cortex (aIC) is a core region that integrates interoceptive states and emotional awareness and consequently guides behavioral responses. Here, we demonstrate that the right-side aIC CamKII⁺ (aIC^CamKII) neurons in mice are activated by aversive visceral signals. Hyperactivation of the right-side aIC^CamKII neurons attenuates food consumption, while inhibition of these neurons increases feeding and reverses aversive stimuli-induced anorexia and weight loss. Similar manipulation at the left-side aIC does not cause significant behavioral changes. Furthermore, virus tracing reveals that aIC^CamKII neurons project directly to the vGluT2⁺ neurons in the lateral hypothalamus (LH), and the right-side aIC^CamKII-to-LH pathway mediates feeding suppression. Our studies uncover a circuit from the cortex to the hypothalamus that senses aversive visceral signals and controls feeding behavior.