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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Summary: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.
ISSN:2041-1723