Early impact of a diabetes inducing high-fructose diet on olfaction in mice

The influence of nutritional status on olfactory processes has been thoroughly investigated over the last few years. It is now well-established that both nutritional status and hormones implicated in food metabolism can effectively modulate the olfactory system from the single neuron to the behavior. Therefore, it seems likely that metabolic disorders such as type 2 diabetes (T2D) can induce olfactory dysfunctions. Indeed T2D patients display poor olfactory performances although the direct effects of diabetes on olfaction were not yet demonstrated. Here, we investigated the modulation of olfaction in young adult (5 weeks old) C57Bl/6 male mice caused by a high-fructose diet (HFruD), known to induce T2D in rodents. The development of T2D was monitored by metabolic approaches (weight gain, food and water intake, glycemia, insulinemia and glucose tolerance test). Animals displayed hyperglycemia, hyperinsulinemia and glucose intolerance after only 4 weeks of HFruD indicating a prediabetic state. In addition, after 4 weeks of HFruD, animals exhibited a decrease in olfactory capacities for both neutral and food odors (assessed by habituation / dishabituation test and buried food test respectively). General electrical responses of the olfactory mucosa (measured by electro-olfactogram) were reduced in HFruD animals. These behavioral and physiological effects persisted after 8 weeks of HFruD. Using immunohistochemistry, we observed a reduction of apoptosis in the olfactory mucosa indicating that HFruD modifies cell dynamics. Our results demonstrate that olfaction is modified by HFruD in rodents. Functional, anatomical and behavioral changes occurred in the olfactory system even before the complete development of the disease. Our data suggest that olfactory dysfunctions may be due to metabolic changes during the onset of T2D