Editors' ChoiceObesity

Hold your nose to get lean

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Science Translational Medicine  26 Jul 2017:
Vol. 9, Issue 400, eaao0974
DOI: 10.1126/scitranslmed.aao0974


Decreased olfactory function is associated with lean phenotype, improved peripheral metabolism, and increased energy expenditure during a high-fat diet.

The sense of smell is powerful. Whether an unpleasant odor elicits a feeling of nausea or a pleasant smell evokes a vivid memory, olfaction can modulate potent systemic responses. Smelling food in the absence of consumption can also alter the activation of hypothalamic neurons involved in the release of metabolic hormones. Although the mechanisms that mediate the effect of olfaction on metabolism are unclear, olfactory sensory neurons may prime metabolic systems for food consumption through either direct or indirect circuits.

To explore these relationships, Riera et al. first leveraged mouse models of olfactory neuron loss. Conditional ablation of olfactory neurons using an inducible diphtheria toxin receptor resulted in reduced olfactory capacity (hyposmia) in adult animals. This loss of smell sensitivity blunted high-fat diet–induced weight gain and decreased both fat mass and food intake. Measures of oxygen consumption and heat production in these mice suggested that the blunted sense of smell was also associated with increased energy expenditure. Hyposmic, high-fat fed animals also had lower concentrations of circulating free fatty acids, leptin, and inflammatory markers, as well as improved glucose tolerance and insulin sensitivity compared with controls. These animals also exhibited indexes of increased thermogenesis, suggesting that the decreased weight gain in hyposmic animals was due to a combination of reduced food intake and increased metabolism. Use of a more specific olfactory sensory neuron ablation model showed consistent metabolic benefits; olfactory inhibition decreased adiposity and improved glucose tolerance and insulin sensitivity in high-fat fed animals with no effect on food intake. Investigators then induced increased smell sensitivity (hyperosmia) in mice by ablating insulin-like growth factor 1 receptors in the main olfactory endothelium. Hyperosmic mice showed markers of impaired metabolism, including age-dependent weight gain, increased adiposity despite similar food intake, and impaired insulin-mediated suppression of glucose release by the liver.

The findings from these new models exploring metabolic effects of altered olfactory function suggest that the sense of smell has a powerful effect on modulating peripheral metabolism. This study lays the foundation for future work to investigate therapeutic approaches targeting the olfactory system in individuals with metabolic diseases such as obesity and diabetes.

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