213-LB: Identification of Olfactory Circuits Modulating Energy Homeostasis

Olfactory inputs are important for hedonic evaluation of food, resulting in food choice and possible consumption. The hypothalamus is a master regulator of whole-body energy homeostasis, integrating internal and external stimuli to modulate energy intake and expenditure accordingly. However, how the hypothalamus adjusts circuits regulating energy homeostasis depending on external stimuli, such as smell, remains an intriguing mystery. Here, we determined the role of olfactory inputs on energy homeostasis by using chemogenetic approach and chemical ablation of OSN to inhibit or stimulate olfaction. Acute inhibition of olfaction changed gene expression of some key neuropeptides in hypothalamus in fasted and refed mice. Chronic silencing of mitral cells in OB promotes resistance to diet-induced obesity, mainly by decreasing food intake. Additionally, chemical ablation of mature OSNs decreases neuronal activity in olfactory cortex and in ARC suggesting that loss of smell, in addition to impacting olfactory pathways, also affects neuronal activity in the ARC, and therefore is likely to alter energy homeostasis. Acute stimulation of mitral cells layer in OB increases neuronal activity in ARC as well as dorsomedial hypothalamus (DMH). Observed increase in ARC neuronal activity is mainly due to activation of glutaminergic neurons. Acute stimulation of olfaction led to increased oxygen consumption and heat production, with no changes observed upon chronic stimulation. Further studies are required to determine specific neuronal cell types within the ARC and DMH that respond to inhibition/stimulation of olfaction and therefore modulating energy homeostasis.