Editors' ChoiceMetabolism

Olfactory control of metabolism

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Sci. Signal.  25 Jul 2017:
Vol. 10, Issue 489, eaao4413
DOI: 10.1126/scisignal.aao4413

Activation of olfactory sensory neurons promotes adiposity and insulin resistance in mice.

The scent of food is important for the perception of flavor and triggers physiological responses that prepare the body for a meal, such as increased secretion of saliva and gastric acid. Riera et al. report that the sense of smell also affects metabolism. OMPDTR mice, in which olfactory sensory neurons (OSNs) were selectively ablated by treating young animals with diphtheria toxin, did not gain as much weight as did wild-type mice when fed a high-fat diet (HFD), and they exhibited improved glucose tolerance and insulin sensitivity relative to controls. The difference in weight was due to reduced fat mass, whereas lean mass was similar between the two groups. Surprisingly, ablation of OSNs reduced the fat mass in mice that were already obese because of a HFD and prevented additional weight gain upon continued HFD feeding. Although OMPDTR mice consumed slightly less food than did their control littermates on a HFD, they did not exercise more than control mice nor did they show any defects in nutrient absorption. Instead, the OMPDTR mice consumed more oxygen and expended more energy, particularly in brown adipose tissue and subcutaneous fat. Thermogenesis was increased in the adipose tissue of OMPDTR mice due to the increased stimulation of adipocytes by the sympathetic nervous system. Mice engineered to have reduced insulin signaling in the olfactory epithelium exhibited increased olfactory sensitivity as measured by their enhanced ability to locate hidden food or urine. Compared with controls, these hyperosmic mice exhibited increased fat mass, insulin resistance, and reduced hepatic glucose production when maintained on a normal diet. Thus, the olfactory system influences metabolism beyond simply affecting appetite. Precisely how OSNs stimulate the autonomic nervous system to elicit metabolic changes remains to be determined, but evidence from this study suggests that these responses may be mediated by neurons that produce the neuropeptides AgRP and POMC.

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