Regulation of Metabolic Health by an "Olfactory-Hypothalamic Axis" and Its Possible Implications for the Development of Therapeutic Approaches for Obesity and T2D.

The olfactory system is responsible for the reception, integration and interpretation of odors. However, in the last years, it has been discovered that the olfactory perception of food can rapidly modulate the activity of hypothalamic neurons involved in the regulation of energy balance. Conversely, the hormonal signals derived from changes in the metabolic status of the body can also change the sensitivity of the olfactory system, suggesting that the bidirectional relationship established between the olfactory and the hypothalamic systems is key for the maintenance of metabolic homeostasis. In the first part of this review, we describe the possible mechanisms and anatomical pathways involved in the modulation of energy balance regulated by the olfactory system. Hence, we propose a model to explain its implication in the maintenance of the metabolic homeostasis of the organism. In the second part, we discuss how the olfactory system could be involved in the development of metabolic diseases such as obesity and type two diabetes and, finally, we propose the use of intranasal therapies aimed to regulate and improve the activity of the olfactory system that in turn will be able to control the neuronal activity of hypothalamic centers to prevent or ameliorate metabolic diseases.