Abstract
Olfactory dysfunction could be an early indicator of cognitive decline in type 2 diabetes (T2D). However, whether obesity affects olfaction in people with T2D is unclear. This question needs to be addressed, because most people with T2D are obese. Importantly, whether different contributing factors leading to obesity (e.g., different components of diet or gain in weight) affect specific olfactory functions and underlying mechanisms is unknown. We examined whether two T2D-inducing obesogenic diets, one containing a high proportion of fat (HFD) and one with moderate fat and high sugar (Western diet, WD), affect odor detection/discrimination, odor-related learning, and olfactory memory in the mouse. We also investigated whether the diets impair adult neurogenesis, GABAergic interneurons, and neuroblasts in the olfactory system. Here, we further assessed olfactory cortex volume and cFos expression-based neuronal activity. The WD-fed mice showed declined odor-related learning and olfactory memory already after 3 months of diet intake (p = 0.046), although both diets induced similar hyperglycemia and weight gain compared to those of standard diet-fed mice (p = 0.0001 and p < 0.0001, respectively) at this time point. Eight months of HFD and WD diminished odor detection (p = 0.016 and p = 0.045, respectively), odor-related learning (p = 0.015 and p = 0.049, respectively), and olfactory memory. We observed no changes in the investigated cellular mechanisms. We show that the early deterioration of olfactory parameters related to learning and memory is associated with a high content of sugar in the diet rather than with hyperglycemia or weight gain. This finding could be exploited for understanding, and potentially preventing, cognitive decline/dementia in people with T2D. The mechanisms behind this finding remain to be elucidated.
Highlights
Olfaction, by influencing vital activities such as food intake, social behavior, and reproduction, plays a crucial role in animal behavior
We recorded a significant increase in homeostatic model assessment for insulin resistance (HOMA-IR) in HFD-fed mice compared to that of WD-fed mice (p = 0.0175) (Figure 1I)
Odorrelated learning and long-term olfactory memory were impaired earlier in the WD group, after only 3 months. Both body weight and hyperglycemia were similar in HFD- and WD-fed mice suggesting that the sugar content in WD, rather than the weight gain per se or differences in blood glucose, is associated with deficits in odor-related learning and olfactory memory
Summary
By influencing vital activities such as food intake, social behavior, and reproduction, plays a crucial role in animal behavior This behavior is partially driven by olfactory networks that are involved in detection and processing of changes in the surrounding chemical environment.[1,2] Olfactory impairment is a predictor of several neurodegenerative diseases.[3] The olfactory system is tightly linked with the endocrine system,[4] and not surprisingly, impaired olfaction has been observed in people with diabetes[5] who show reduced odor detection (ability to detect odors) and odor discrimination (ability to discriminate odors), loss of olfactory memory (ability to recall previously learned odors), and increased risk for anosmia (loss of the sense of smell).[6−9]. Some showed no correlation between BMI and olfactory scores,[6,7,18] while
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