Hypothalamic neuronal activation in primates drives naturalistic goal-directed eating behavior

Ha, L. J.; Yeo, H.-G.; Kim, Y. G.; Baek, I.; Baeg, E.; Lee, Y. H.; Won, J.; Jung, Y.; Park, J.; Jeon, C.-Y.; Kim, K.; Min, J.; Song, Y.; Park, J.-H.; Nam, K. R.; Son, S.; Yoo, S. B. M.; Park, S.-H. M.; Choi, W. S.; Lim, K. S.; Choi, J. Y.; Cho, J.-H.; Lee, Y.; Choi, H. J.

doi:10.1101/2023.06.11.544288

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bioRxiv · 10.1101/2023.06.11.544288

Hypothalamic neuronal activation in primates drives naturalistic goal-directed eating behavior

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Abstract

Eating addiction is the primary cause of modern obesity. Although the causal role of the lateral hypothalamic area (LHA) for eating is demonstrated in rodents, there is no evidence in primates regarding naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating by chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, which was specific for palatable food. PET and MRS validated the chemogenetic activation. Rs-fMRI result revealed that functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after the LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

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Ha, L. J., Yeo, H.-G., Kim, Y. G., Baek, I., Baeg, E., Lee, Y. H., Won, J., Jung, Y., Park, J., Jeon, C.-Y., Kim, K., Min, J., Song, Y., Park, J.-H., Nam, K. R., Son, S., Yoo, S. B. M., Park, S.-H. M., Choi, W. S., Lim, K. S., Choi, J. Y., Cho, J.-H., Lee, Y., Choi, H. J.. 2023-06-12. Hypothalamic neuronal activation in primates drives naturalistic goal-directed eating behavior. https://doi.org/10.1101/2023.06.11.544288

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