INSULIN MODULATES FOOD VALENCE THROUGH ASTROCYTES

Brain cells involved in assigning affective value (i.e.: valence) to stimuli modulating brain states are not yet fully identified. Since astrocytes modulate brain states, and insulin regulates feeding behavior and exerts its central actions in part through astrocytes, we analyzed the role of the insulin receptor in astrocytes in assigning valence to food. We used the modulatory actions of food on anxiety and fear, as proxies of the affective influence of food on mood. Mice lacking insulin receptors (IR) in GFAP astrocytes (GFAP-IR KO mice) showed increased anxiety and fear in response to food, while control littermates showed the opposite behavior. Since orexin neurons in the lateral hypothalamus (LH) are involved in fear conditioning, and are inhibited by feeding, we determined whether they are involved in mood alterations observed in fear-conditioned fed GFAP-IR KO mice. We observed increased c-fos expression in orexin neurons of these animals, indicating that the lack of IR in astrocytes modifies the response of these neurons to food. Moreover, chemogenetic stimulation of LH astrocytes in fed GFAP-IR KO mice was sufficient to significantly attenuate their fear responses. These findings suggest that astrocytic insulin receptors modulate the responses of hypothalamic orexin neurons to food. We speculate that cellular mechanisms underlying eating disorders may involve insulin modulation of food valence through astrocytes.