The Sense of Smell Impacts Metabolic Health and Obesity

Abstract

Olfactory inputs help coordinate food appreciation and selection, but their role in systemic physiology and energy balance is poorly understood. Here we demonstrate that mice upon conditional ablation of mature olfactory sensory neurons (OSNs) are resistant to diet-induced obesity accompanied by increased thermogenesis in brown and inguinal fat depots. Acute loss of smell perception after obesity onset not only abrogated further weight gain but also improved fat mass and insulin resistance. Reduced olfactory input stimulates sympathetic nerve activity, resulting in activation of β-adrenergic receptors on white and brown adipocytes to promote lipolysis. Conversely, conditional ablation of the IGF1 receptor in OSNs enhances olfactory performance in mice and leads to increased adiposity and insulin resistance. These findings unravel a new bidirectional function for the olfactory system in controlling energy homeostasis in response to sensory and hormonal signals.

Linking smell to metabolism and aging

“…To address this question, a recent study manipulated the olfactory system in the mouse and measured the effect on energy homeostasis (2). By ablating olfactory sensory neurons in adult mice, they generated mice that had a reduced ability to smell.…”

“…These mice exhibited increased body weight in the absence of any change in food intake (2). Together, these observations reveal that the olfactory system can regulate body weight via direct effects on energy expenditure, rather than solely through changes in food intake as has traditionally been assumed.…”

“…For example, it is unclear whether the metabolic responses to manipulations of the olfactory system (2, 3) are due to specific changes in the sensing of food odors, and, if so, which food odors are involved. It is likewise unknown how detection of food odors is communicated from the olfactory bulb to the hypothalamic circuits that regulate energy balance, and what specific information these signals convey (e.g., nutrient content, toxicity, availability).…”

Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta‐Analysis of 19 005 Individuals

“…Haploreg shows eQTL hits for NLRP3 in blood and liver tissues, adding strength to our hypothesis that these SNPs may be sharing a regulatory element affecting expression of the NLRP3 gene. The olfactory system is an emerging process that may interact with the endocrine system to impact metabolic health . Olfactory inputs help coordinate food selection and hormonal responses to impact energy homeostasis, adiposity, and insulin resistance .…”

“…The olfactory system is an emerging process that may interact with the endocrine system to impact metabolic health . Olfactory inputs help coordinate food selection and hormonal responses to impact energy homeostasis, adiposity, and insulin resistance . Conditional ablation of the insulin‐like growth factor‐1 receptor in olfactory sensory neurons enhance olfactory performance in mice and leads to increased adiposity and insulin resistance unraveling a new bidirectional function for the olfactory system in controlling energy homeostasis in response to sensory and hormonal signals .…”