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

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 () and Yang He ()
Additional contact information
Yao Liu: Texas Children’s Hospital
Hailan Liu: Baylor College of Medicine
Huey-Xian Kelly Wong: Texas Children’s Hospital
Niccole Auld: Baylor College of Medicine
Kristine M. Conde: Baylor College of Medicine
Yongxiang Li: Baylor College of Medicine
Meng Yu: Baylor College of Medicine
Yue Deng: Baylor College of Medicine
Qingzhuo Liu: Baylor College of Medicine
Xing Fang: Texas Children’s Hospital
Mengjie Wang: Baylor College of Medicine
Yuhan Shi: Baylor College of Medicine
Olivia Z. Ginnard: Baylor College of Medicine
Yuxue Yang: Baylor College of Medicine
Longlong Tu: Baylor College of Medicine
Hesong Liu: Baylor College of Medicine
Jonathan C. Bean: Baylor College of Medicine
Junying Han: Baylor College of Medicine
Megan E. Burt: Baylor College of Medicine
Sanika V. Jossy: Baylor College of Medicine
Yongjie Yang: Baylor College of Medicine
Chunmei Wang: Baylor College of Medicine
Qingchun Tong: University of Texas Health Science Center at Houston
Benjamin R. Arenkiel: Texas Children’s Hospital
Hongjie Li: Baylor College of Medicine
Yong Xu: Baylor College of Medicine
Yang He: Texas Children’s Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63170-2

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