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Publication : Hunger signalling in the olfactory bulb primes exploration, food-seeking and peripheral metabolism.

First Author  Stark R Year  2024
Journal  Mol Metab Volume  89
Pages  102025 PubMed ID  39236785
Mgi Jnum  J:370183 Mgi Id  MGI:7749546
Doi  10.1016/j.molmet.2024.102025 Citation  Stark R, et al. (2024) Hunger signalling in the olfactory bulb primes exploration, food-seeking and peripheral metabolism. Mol Metab 89:102025
abstractText  OBJECTIVE: Although the metabolic state of an organism affects olfactory function, the precise mechanisms and their impact on behavior and metabolism remain unknown. Here, we assess whether ghrelin receptors (GHSRs) in the olfactory bulb (OB) increase olfactory function and influence foraging behaviors and metabolism. METHODS: We performed a detailed behavioural and metabolic analysis in mice lacking GHSRs in the OB (OB(GHSR) deletion). We also analsyed OB scRNA-seq and spatial transcriptomic datasets to assess GHSR+ cells in the main and accessory olfactory bulbs, as well as the anterior olfactory nucleus. RESULTS: OB(GHSR) deletion affected olfactory discrimination and habituation to both food and non-food odors. Anxiety-like and depression-like behaviors were significantly greater after OB(GHSR) deletion, whereas exploratory behavior was reduced, with the greatest effect under fasted conditions. OB(GHSR) deletion impacted feeding behavior as evidenced by altered bout number and duration, as well as buried food-seeking. OB(GHSR) deletion increased body weight and fat mass, spared fat utilisation on a chow diet and impaired glucose metabolism indicating metabolic dysfunction. Cross referenced analysis of OB scRNA-seq and spatial transcriptomic datasets revealed GHSR+ glutamate neurons in the main and accessory olfactory bulbs, as well as the anterior olfactory nucleus. Ablation of glutamate neurons in the OB reduced ghrelin-induced food finding and phenocopied results seen after OB(GHSR) deletion. CONCLUSIONS: OB(GHSRs) help to maintain olfactory function, particularly during hunger, and facilitate behavioral adaptations that optimise food-seeking in anxiogenic environments, priming metabolic pathways in preparation for food consumption.
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