High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice

Abstract

Type 2 Diabetes (T2D), a major public health issue reaching worldwide epidemic, has been correlated with lower olfactory abilities in humans. As olfaction represents a major component of feeding behavior, its alteration may have drastic consequences on feeding behaviors that may in turn aggravates T2D. In order to decipher the impact of T2D on the olfactory epithelium, we fed mice with a high fructose diet (HFruD) inducing early diabetic state in 4 to 8 weeks. After only 4 weeks of this diet, mice exhibited a dramatic decrease in olfactory behavioral capacities. Consistently, this decline in olfactory behavior was correlated to decreased electrophysiological responses of olfactory neurons recorded as a population and individually. Our results demonstrate that, in rodents, olfaction is modified by HFruD-induced diabetes. Functional, anatomical and behavioral changes occurred in the olfactory system at a very early stage of the disease.

Type 2 diabetes impairs odour detection, olfactory memory and olfactory neuroplasticity; effects partly reversed by the DPP-4 inhibitor Linagliptin

“…We also provide, for the first time, experimental evidence that olfactory memory is strongly impaired in T2D. Interestingly, recent works showed that hyperlipidemic and fructose-based diets disrupt odour-related learning [ 48 , 74 , 87 ]. These findings could be relevant for the understanding of the interplay between T2D and cognitive decline/dementia and they call for new clinical studies aimed at determining whether olfactory memory is impaired in T2D patients and, if so, whether this impairment correlates with the incidence of cognitive decline and dementia.…”

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

“… 23 Rivière and colleagues showed decreased odor detection and impaired odor discrimination in early diabetic mice fed with a diet based on high fructose for 4 weeks. 27 Moreover, results of an interesting study by Tucker and colleagues showed impairment in the detection of fatty scents, but not sweet scents, induced by 6.5 months of moderately HFD intake. 25 Authors interpreted these data as resulting from negative alliesthesia (sensation change from pleasure to displeasure), not odor detection impairment.…”

“… 26 OSNs in mice fed with a high fructose diet showed a decreased response to odorant stimulation and reduced excitability. 27 Riera et al reported that obesity-induced loss of smell perception normalized body mass and improved insulin resistance, and loss of IGF1 receptors in OSNs improved olfactory functions in mice. 55 However, others have suggested that olfactory dysfunction is also present in HFD-fed, nonobese mice.…”

All You Can Feed: Some Comments on Production of Mouse Diets Used in Biomedical Research with Special Emphasis on Non-Alcoholic Fatty Liver Disease Research

“…Feeding of fructose in combination with fat and cholesterol for four days was already sufficient to induce hepatic triglyceride accumulation demonstrating that individual "unhealthy" compounds within a diet can be additive or synergistic [138]. Moreover, the feeding of fructose (60%) for four to eight weeks provoked impairment of olfactory epithelium, resulting in reduced olfactory behavioral capacities [139].…”