Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake

Rea, J. J.; Liu, C. M.; Hayes, A. M. R.; Ohan, R.; Schwartz, G. M.; Bashaw, A. G.; Klug, M. E.; Decarie-Spain, L.; Park, Y.; Kao, A. E.; Grinevich, V.; Kanoski, S. E.

doi:10.1101/2024.11.20.624599

bioRxiv · 10.1101/2024.11.20.624599

Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake

Rea, J. J.·Liu, C. M.·Hayes, A. M. R.·Ohan, R.·Schwartz, G. M.·Bashaw, A. G.·Klug, M. E.·Decarie-Spain, L.·Park, Y.·Kao, A. E.·Grinevich, V.·Kanoski, S. E.

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Abstract

Oxytocin (OT) is a neuropeptide produced in the paraventricular (PVH) and supraoptic (SON) nuclei of the hypothalamus. Either peripheral or central administration of OT suppresses food intake through reductions in meal size. However, pharmacological approaches do not differentiate whether observed effects are mediated by OT neurons located in the PVH or in the SON. To address this, we targeted OT neuron-specific designer receptors exclusively activated by designer drugs (DREADDs) in either the PVH or SON in rats, thus allowing for evaluation of food intake following selective activation of OT neurons separately in each nucleus. Results revealed that DREADDs-mediated excitation of PVH OT neurons reduced consumption of both standard chow and a high fat high sugar diet (HFHS) via reductions in meal size. On the contrary, SON OT neuron activation had the opposite effect by increasing both standard chow and liquid sucrose consumption, with the former effect mediated by an increase in meal size. To further examine the physiological role of OT neurons in eating behavior, a viral-mediated approach was used to silence synaptic transmission of OT neurons separately in either the PVH or SON. Results from these studies revealed that PVH OT neuron silencing significantly increased consumption of HFHS by increasing meal size whereas SON OT neuron silencing reduced chow consumption by decreasing meal size. Collectively these data reveal that PVH and SON OT neurons differentially modulate food intake by either increasing or decreasing satiation signaling, respectively.

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Rea, J. J., Liu, C. M., Hayes, A. M. R., Ohan, R., Schwartz, G. M., Bashaw, A. G., Klug, M. E., Decarie-Spain, L., Park, Y., Kao, A. E., Grinevich, V., Kanoski, S. E.. 2024-11-21. Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake. https://doi.org/10.1101/2024.11.20.624599

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