Western Diet Accelerates the Impairment of Odor-Related Learning and Olfactory Memory in the Mouse

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.

Olfaction in the context of obesity and diabetes: Insights from animal models to humans

“…Very few studies have examined neuroplasticity associated with metabolic diseases in the PCx. No effect on the volume of the PCx nor on the neuronal activation of piriform neurons assessed using c-fos were reported after 8 months of HFD (Lietzau et al, 2020). However, in T2D Goto-Kakizaki rats, (Lietzau et al, 2018) observed a decrease in parvalbumin expression and impairment of neuroblast differentiation in the PCx.…”

“…Under olfactory activation, juxta-glomerular cells surrounding the lateral glomerulus exhibited a loss of activity that was stronger for HFD than for mild FD, whereas juxta-glomerular cells surrounding the medial glomerulus were equally impaired for both diets (Fardone et al, 2019). No effect in MOB neurogenesis was reported after 8 months of HFD (Lietzau et al, 2020), on the other hand, a reduction of neurogenesis was reported in the T2D model of Goto-Kakizaki rats (Lietzau et al, 2018). Furthermore, (Soleimanzad et al, 2019) examined resting state and odor-evoked hemodynamic profiles in the MOB of 3 months and 8 months HFD-fed mice by laser speckle contrast imaging.…”

“…After 1 month of HFD or western diet, no difference in the olfactory performances was observed compared to a regular diet fed group. After 3 months of diet, the HFD group started to spend more time to find a buried food (a piece of a protein bar), and the difference was significant for the 2 groups (HFD and western diet) after 8 months of diet (Lietzau et al, 2020). Another study in mice revealed different outcomes according to the sensory properties of the food used in the test (Tucker et al, 2012b).…”

Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice

“…Nevertheless, TRF introduces a significant modification in olfactory detection ability emphasised in the HFD group with TM and TRF. As HFD causes deterioration of odour recognition, odour discrimination and odour-dependent learning, TRF restores olfactory odour recognition [ 63 ]. In this context, an increase of olfactory sensitivity was observed in rats by an intracerebroventricular injection with orexin, an anorexigenic molecule imitating a fasting state [ 64 ].…”

Crème de la Créature: Dietary Influences on Behavior in Animal Models

“…In mice, a high fat diet also blunted olfactory responses (Takase et al, 2016 ), olfactory discrimination, and promoted the loss of olfactory neurons and their axons (Thiebaud et al, 2014 ). These alterations in chemosensation could impair reward learning, a crucial component of satiation, and interestingly, defects in cue-reward learning have been observed in rodents fed high fat or human processed food diets (Swithers and Davidson, 2008 ; Davidson et al, 2014 ; Thiebaud et al, 2014 ; Lietzau et al, 2020 ).…”