The local GLP-1 system in the olfactory bulb is required for odor-evoked cephalic phase of insulin release in mice

Montaner, M. Villalba; Denom, Jessica; Jiang, Wanqing; Magnan, Christophe; Trapp, Stefan; Gurden, Hirac

doi:10.1016/j.molmet.2023.101738

Cited by 6 publications

(2 citation statements)

References 65 publications

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“…Among locally produced neuropeptides that modulate olfactory processing by acting on their respective receptors in the OB are somatostatin and glucagon-like peptide 1 (GLP-1). 54 Oxytocin is a hormone produced in the hypothalamus, and oxytocin receptors are found in the OB 55,56 and adjacent AON 57 suggesting oxytocin may influence social behaviour by regulating olfactory processes. Further, orexinpositive fibres, originating from cell bodies in the lateral hypothalamus (LH), have been found in the OB.…”

Section: Extrinsic Modulationmentioning

confidence: 99%

“…170 Moreover, GLP-1 signalling in the OB boosted olfactory function in obese mice by restoring the loss of foraging behaviour and enhancing odour-induced insulin release in the cephalic phase. 54 The injection of GLP-1 antagonist exendin-9 in the OB of lean mice impaired food retrieval time in a buried foodfinding test, whereas the agonist Exendin-4 rescued the lack of foraging behaviour of obese mice and increased olfactory sensitivity.…”

Section: Anorexigenic Hormonesmentioning

confidence: 99%

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The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism

Stark

2024

J Neuroendocrinology

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Olfaction is the most ancient sense and is needed for food‐seeking, danger protection, mating and survival. It is often the first sensory modality to perceive changes in the external environment, before sight, taste or sound. Odour molecules activate olfactory sensory neurons that reside on the olfactory epithelium in the nasal cavity, which transmits this odour‐specific information to the olfactory bulb (OB), where it is relayed to higher brain regions involved in olfactory perception and behaviour. Besides odour processing, recent studies suggest that the OB extends its function into the regulation of food intake and energy balance. Furthermore, numerous hormone receptors associated with appetite and metabolism are expressed within the OB, suggesting a neuroendocrine role outside the hypothalamus. Olfactory cues are important to promote food preparatory behaviours and consumption, such as enhancing appetite and salivation. In addition, altered metabolism or energy state (fasting, satiety and overnutrition) can change olfactory processing and perception. Similarly, various animal models and human pathologies indicate a strong link between olfactory impairment and metabolic dysfunction. Therefore, understanding the nature of this reciprocal relationship is critical to understand how olfactory or metabolic disorders arise. This present review elaborates on the connection between olfaction, feeding behaviour and metabolism and will shed light on the neuroendocrine role of the OB as an interface between the external and internal environments. Elucidating the specific mechanisms by which olfactory signals are integrated and translated into metabolic responses holds promise for the development of targeted therapeutic strategies and interventions aimed at modulating appetite and promoting metabolic health.

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Section: Extrinsic Modulationmentioning

confidence: 99%

Section: Anorexigenic Hormonesmentioning

confidence: 99%

The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism

Stark

2024

J Neuroendocrinology

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GLP-1 programs the neurovascular landscape

Chen,

Yu,

Horvath-Diano

et al. 2024

Cell Metabolism

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A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

Montaner,

Denom,

Simon

et al. 2024

Nat Commun

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Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α 2 -adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABA A receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

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The local GLP-1 system in the olfactory bulb is required for odor-evoked cephalic phase of insulin release in mice

Cited by 6 publications

References 65 publications

The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism

The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism

GLP-1 programs the neurovascular landscape

A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

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