Olfaction is closely linked to energy homeostasis regulation. The olfactory system shares several molecular, anatomical and functional links with brain areas and peripheral organs involved in food intake and body weight regulations. We demonstrated that the feeding state modulates olfactory detection: fasted rats display better olfactory sensitivity that satiated ones. This modulation is also observed in Obese Zucker fa/fa rats. However, obesity-resistant LouC rats do not modulate their olfactory detection according to the feeding state. Peripheral hormones and neuropeptides involved in energy homeostasis regulation might be responsible for olfactory detection modulation. To examine this hypothesis, we evaluated the respective roles of Orexin A, a hypothalamic orexigenic neuropeptide; as well as leptin and insulin, two peripheral adiposity hormones; on olfactory detection. We demonstrated that central administration of Orexin A increases olfactory detection; whereas central administration of leptin or insulin decreases olfactory detection. Orexin A, leptin and insulin receptors are widely expressed in the olfactory system. We further demonstrated that insulin receptors were abundantly expressed in discrete olfactory bulb areas and in several neuron types of the olfactory bulb network. The whole of these data, supported by several reports, suggest that hormones and neuropeptides classically involved in energy homeostasis regulation extend their roles to olfactory detection modulation. Indeed, orexigenic signals released upon fasting or in conditions of energy depletion increase olfactory detection which participate in meal initiation. By contrast, anorexigenic signals released during refeeding or in conditions of energy abundance decrease olfactory detection which participate in meal termination. With the ever rising incidence of metabolic disorders, elucidating the cross-talks between olfaction and energy homeostasis regulation is of critical relevance to better understand and manage the etiology of altered food-intake behaviours.
