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

Romana Stark, Harry Dempsey, Elizabeth Kleeman, Martina Sassi, Sherri Osborne-Lawrence, Sepideh Sheybani-Deloui, Karl Austin-Muttitt, Jonathan Mullins Orcid Logo, Jeffrey M Zigman, Jeffrey Davies Orcid Logo, Zane B Andrews

Molecular metabolism

Swansea University Authors: Martina Sassi, Karl Austin-Muttitt, Jonathan Mullins Orcid Logo, Jeffrey Davies Orcid Logo

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Abstract

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 behavio...

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Published in: Molecular metabolism
ISSN: 2212-8778
Published: Elsevier 2024
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa67734
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Abstract: 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 (OBGHSR 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 OBGHSR deletion affected olfactory discrimination and habituation to both food and non-food odors. Anxiety-like and depression-like behaviors were significantly greater after OBGHSR deletion, whereas exploratory behavior was reduced, with the greatest effect under fasted conditions. OBGHSR deletion impacted feeding behavior as evidenced by altered bout number and duration, as well as buried food-seeking. OBGHSR 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 OBGHSR deletion. Conclusions OBGHSRs 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.
College: Faculty of Medicine, Health and Life Sciences
Funders: National Health and Medical Research Council of Australia APP1154974; APP1125960 (ZBA); APP1160065 (RS). Phenomics Australia is supported by the Australian Government Department of Education through the National Collaborative Research Infrastructure Strategy, the Super Science Initiative and the Collaborative Research Infrastructure Scheme.