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

Objectives: Oxytocin (OT) is a neuropeptide produced in the paraventricular (PVH) and supraoptic (SON) nuclei of the hypothalamus. Either peripheral or central OT administration reduces food intake through reductions in meal size. However, pharmacological approaches do not differentiate whether OT&#...

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Main Authors: Jessica J. Rea, Clarissa M. Liu, Anna M.R. Hayes, Rita Ohan, Grace M. Schwartz, Alexander G. Bashaw, Molly E. Klug, Lea Decarie-Spain, Yedam Park, Alicia E. Kao, Valery Grinevich, Scott E. Kanoski
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Molecular Metabolism
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Online Access:http://www.sciencedirect.com/science/article/pii/S2212877825001279
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author Jessica J. Rea
Clarissa M. Liu
Anna M.R. Hayes
Rita Ohan
Grace M. Schwartz
Alexander G. Bashaw
Molly E. Klug
Lea Decarie-Spain
Yedam Park
Alicia E. Kao
Valery Grinevich
Scott E. Kanoski
author_facet Jessica J. Rea
Clarissa M. Liu
Anna M.R. Hayes
Rita Ohan
Grace M. Schwartz
Alexander G. Bashaw
Molly E. Klug
Lea Decarie-Spain
Yedam Park
Alicia E. Kao
Valery Grinevich
Scott E. Kanoski
author_sort Jessica J. Rea
collection DOAJ
description Objectives: Oxytocin (OT) is a neuropeptide produced in the paraventricular (PVH) and supraoptic (SON) nuclei of the hypothalamus. Either peripheral or central OT administration reduces food intake through reductions in meal size. However, pharmacological approaches do not differentiate whether OT's influence on food intake is mediated by OT neurons located in the PVH vs. the SON. Here we address this gap using both gain- and loss-of-function approaches targeting OT neurons. Methods: OT neuron-specific designer receptors exclusively activated by designer drugs (DREADDs) were targeted in either the PVH or SON in rats, thus allowing for evaluation of caloric intake following selective activation of OT neurons separately in each nucleus. To examine the physiological role of distinct OT neuron populations in eating behavior, a viral-mediated approach was used to silence synaptic transmission of OT neurons separately in either the PVH or SON. Results: DREADDs-mediated excitation of PVH OT neurons reduced consumption of standard chow via reductions in meal size. On the contrary, SON OT neuron activation had the opposite effect by increasing standard chow consumption. Consistent with these opposing outcomes, activation of PVH and SON OT neurons simultaneously had minimal effects on food intake. Additional results from chronic loss-of-function experiments reveal that PVH OT neuron silencing significantly increased consumption of a high fat and high sugar diet by increasing meal size whereas SON OT neuron silencing reduced chow consumption by decreasing meal size. Conclusions: Collectively these findings suggest that PVH and SON OT neurons differentially modulate food intake by either reducing or increasing caloric consumption, respectively.
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spelling doaj-art-18afed783c4f4331978cb7f281b18a872025-08-20T03:38:44ZengElsevierMolecular Metabolism2212-87782025-10-0110010222010.1016/j.molmet.2025.102220Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intakeJessica J. Rea0Clarissa M. Liu1Anna M.R. Hayes2Rita Ohan3Grace M. Schwartz4Alexander G. Bashaw5Molly E. Klug6Lea Decarie-Spain7Yedam Park8Alicia E. Kao9Valery Grinevich10Scott E. Kanoski11Human and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USA; Neuroscience Graduate Program, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USA; Neuroscience Graduate Program, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USA; Neuroscience Graduate Program, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USAHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USADepartment of Neuropeptide Research for Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), University of Heidelberg, Mannheim, GermanyHuman and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, USA; Neuroscience Graduate Program, University of Southern California, USA; Corresponding author. 3616 Trousdale Parkway, AHF-252, Los Angeles, CA 90089-0372, USA.Objectives: Oxytocin (OT) is a neuropeptide produced in the paraventricular (PVH) and supraoptic (SON) nuclei of the hypothalamus. Either peripheral or central OT administration reduces food intake through reductions in meal size. However, pharmacological approaches do not differentiate whether OT's influence on food intake is mediated by OT neurons located in the PVH vs. the SON. Here we address this gap using both gain- and loss-of-function approaches targeting OT neurons. Methods: OT neuron-specific designer receptors exclusively activated by designer drugs (DREADDs) were targeted in either the PVH or SON in rats, thus allowing for evaluation of caloric intake following selective activation of OT neurons separately in each nucleus. To examine the physiological role of distinct OT neuron populations in eating behavior, a viral-mediated approach was used to silence synaptic transmission of OT neurons separately in either the PVH or SON. Results: DREADDs-mediated excitation of PVH OT neurons reduced consumption of standard chow via reductions in meal size. On the contrary, SON OT neuron activation had the opposite effect by increasing standard chow consumption. Consistent with these opposing outcomes, activation of PVH and SON OT neurons simultaneously had minimal effects on food intake. Additional results from chronic loss-of-function experiments reveal that PVH OT neuron silencing significantly increased consumption of a high fat and high sugar diet by increasing meal size whereas SON OT neuron silencing reduced chow consumption by decreasing meal size. Conclusions: Collectively these findings suggest that PVH and SON OT neurons differentially modulate food intake by either reducing or increasing caloric consumption, respectively.http://www.sciencedirect.com/science/article/pii/S2212877825001279FeedingObesityHypothalamusNeuropeptidesOxytocinSatiety
spellingShingle Jessica J. Rea
Clarissa M. Liu
Anna M.R. Hayes
Rita Ohan
Grace M. Schwartz
Alexander G. Bashaw
Molly E. Klug
Lea Decarie-Spain
Yedam Park
Alicia E. Kao
Valery Grinevich
Scott E. Kanoski
Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
Molecular Metabolism
Feeding
Obesity
Hypothalamus
Neuropeptides
Oxytocin
Satiety
title Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
title_full Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
title_fullStr Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
title_full_unstemmed Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
title_short Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
title_sort oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake
topic Feeding
Obesity
Hypothalamus
Neuropeptides
Oxytocin
Satiety
url http://www.sciencedirect.com/science/article/pii/S2212877825001279
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