Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit

Abstract Olfactory perception of food odors is a key determinant of eating behavior, including triggering appetite, facilitating food seeking and influencing food choice. While transient food-related olfactory cues stimulate appetite and provoke cravings in states of hunger, emerging evidence implie...

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Main Authors: Yao Liu, Hailan Liu, Huey-Xian Kelly Wong, Niccole Auld, Kristine M. Conde, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z. Ginnard, Yuxue Yang, Longlong Tu, Hesong Liu, Jonathan C. Bean, Junying Han, Megan E. Burt, Sanika V. Jossy, Yongjie Yang, Chunmei Wang, Qingchun Tong, Benjamin R. Arenkiel, Hongjie Li, Yong Xu, Yang He
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-63170-2
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author Yao Liu
Hailan Liu
Huey-Xian Kelly Wong
Niccole Auld
Kristine M. Conde
Yongxiang Li
Meng Yu
Yue Deng
Qingzhuo Liu
Xing Fang
Mengjie Wang
Yuhan Shi
Olivia Z. Ginnard
Yuxue Yang
Longlong Tu
Hesong Liu
Jonathan C. Bean
Junying Han
Megan E. Burt
Sanika V. Jossy
Yongjie Yang
Chunmei Wang
Qingchun Tong
Benjamin R. Arenkiel
Hongjie Li
Yong Xu
Yang He
author_facet Yao Liu
Hailan Liu
Huey-Xian Kelly Wong
Niccole Auld
Kristine M. Conde
Yongxiang Li
Meng Yu
Yue Deng
Qingzhuo Liu
Xing Fang
Mengjie Wang
Yuhan Shi
Olivia Z. Ginnard
Yuxue Yang
Longlong Tu
Hesong Liu
Jonathan C. Bean
Junying Han
Megan E. Burt
Sanika V. Jossy
Yongjie Yang
Chunmei Wang
Qingchun Tong
Benjamin R. Arenkiel
Hongjie Li
Yong Xu
Yang He
author_sort Yao Liu
collection DOAJ
description Abstract Olfactory perception of food odors is a key determinant of eating behavior, including triggering appetite, facilitating food seeking and influencing food choice. While transient food-related olfactory cues stimulate appetite and provoke cravings in states of hunger, emerging evidence implies that prolonged and sustained exposure to food-derived odor (FO) suppresses feeding. However, the mechanisms by which olfaction induces hypophagia remain elusive. In this study, we show that prolonged FO exposure significantly suppresses food intake in male mice. We identified a subset of neurons in the ventral subiculum (vSub) that are specifically activated by FO. We further discovered that these FO-activated neurons in the vSub receive excitatory inputs from the olfactory bulb (OB) and send glutamatergic projections to the ventromedial hypothalamus (VMH). Inhibition of the OB → vSub → VMH circuit abolished the FO-induced reduction in food intake, while activation of this circuit suppressed feeding and reduced body weight. Together, these findings reveal a neurobiological circuitry that mediates the influence of olfactory signals on food intake regulation.
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series Nature Communications
spelling doaj-art-9187bb82c06443d0981d431ce9b2a1ba2025-08-24T11:37:07ZengNature PortfolioNature Communications2041-17232025-08-0116111710.1038/s41467-025-63170-2Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuitYao Liu0Hailan Liu1Huey-Xian Kelly Wong2Niccole Auld3Kristine M. Conde4Yongxiang Li5Meng Yu6Yue Deng7Qingzhuo Liu8Xing Fang9Mengjie Wang10Yuhan Shi11Olivia Z. Ginnard12Yuxue Yang13Longlong Tu14Hesong Liu15Jonathan C. Bean16Junying Han17Megan E. Burt18Sanika V. Jossy19Yongjie Yang20Chunmei Wang21Qingchun Tong22Benjamin R. Arenkiel23Hongjie Li24Yong Xu25Yang He26Jan and Dan Duncan Neurological Research Institute, Texas Children’s HospitalDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineJan and Dan Duncan Neurological Research Institute, Texas Children’s HospitalProgram in Cancer Cell Biology, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineJan and Dan Duncan Neurological Research Institute, Texas Children’s HospitalDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineBrown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at HoustonJan and Dan Duncan Neurological Research Institute, Texas Children’s HospitalHuffington Center on Aging, Baylor College of MedicineDepartment of Pediatrics, USDA/ARS Children’s Nutrition Research Center, Baylor College of MedicineJan and Dan Duncan Neurological Research Institute, Texas Children’s HospitalAbstract Olfactory perception of food odors is a key determinant of eating behavior, including triggering appetite, facilitating food seeking and influencing food choice. While transient food-related olfactory cues stimulate appetite and provoke cravings in states of hunger, emerging evidence implies that prolonged and sustained exposure to food-derived odor (FO) suppresses feeding. However, the mechanisms by which olfaction induces hypophagia remain elusive. In this study, we show that prolonged FO exposure significantly suppresses food intake in male mice. We identified a subset of neurons in the ventral subiculum (vSub) that are specifically activated by FO. We further discovered that these FO-activated neurons in the vSub receive excitatory inputs from the olfactory bulb (OB) and send glutamatergic projections to the ventromedial hypothalamus (VMH). Inhibition of the OB → vSub → VMH circuit abolished the FO-induced reduction in food intake, while activation of this circuit suppressed feeding and reduced body weight. Together, these findings reveal a neurobiological circuitry that mediates the influence of olfactory signals on food intake regulation.https://doi.org/10.1038/s41467-025-63170-2
spellingShingle Yao Liu
Hailan Liu
Huey-Xian Kelly Wong
Niccole Auld
Kristine M. Conde
Yongxiang Li
Meng Yu
Yue Deng
Qingzhuo Liu
Xing Fang
Mengjie Wang
Yuhan Shi
Olivia Z. Ginnard
Yuxue Yang
Longlong Tu
Hesong Liu
Jonathan C. Bean
Junying Han
Megan E. Burt
Sanika V. Jossy
Yongjie Yang
Chunmei Wang
Qingchun Tong
Benjamin R. Arenkiel
Hongjie Li
Yong Xu
Yang He
Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit
Nature Communications
title Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit
title_full Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit
title_fullStr Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit
title_full_unstemmed Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit
title_short Prolonged exposure to food odors suppresses feeding via an olfactory bulb-to-hypothalamus circuit
title_sort prolonged exposure to food odors suppresses feeding via an olfactory bulb to hypothalamus circuit
url https://doi.org/10.1038/s41467-025-63170-2
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