Loss of odor-induced c-Fos expression of juxtaglomerular activity following maintenance of mice on fatty diets

Abstract

Diet-induced obesity (DIO) decreases the number of OMP+ olfactory sensory neurons (OSN) in the olfactory epithelium by 25% and reduces correlate axonal projections to the olfactory bulb (OB). Whether surviving OSNs have equivalent odor responsivity is largely unknown. Herein, we utilized c-fos immediate-early gene expression to map neuronal activity and determine whether mice weaned to control (CF), moderately-high fat (MHF), or high-fat (HF) diet for a period of 6 months had changes in odor activation. Diet-challenged M72-IRES-tau-GFP mice were exposed to either a preferred M72 (Olfr160) ligand, isopropyl tiglate, or clean air in a custom-made Bell-jar infusion chamber using an alternating odor exposure pattern generated by a picosprizer™. Mice maintained on fatty diets weighed significantly more and cleared glucose less efficiently as determined by an intraperitoneal glucose tolerance test (IPGTT). The number of juxtaglomerular cells (JGs) decreased following maintenance of the mice on the MHF diet for cells surrounding the medial but not lateral M72 glomerulus within a 4 cell-column distance. The percentage of c-fos + JGs surrounding the lateral M72 glomerulus decreased in fat-challenged mice whereas those surrounding the medial glomerulus were not affected by diet. Altogether, these results show an asymmetry in the responsiveness of the 'mirror image' glomerular map for the M72 receptor that shows greater sensitivity of the lateral vs. medial glomerulus upon exposure to fatty diet.

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

“… 24 Moreover, HFD can induce the functional impairment of mitral cells 56 and also reduce the activation of specific populations of neurons (juxtaglomerular/cFos+ cells) in the MOB. 57 …”

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

“…The excitability of those cells is also impaired. 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).…”

“…Similar effects on the mucosa are obtained using a high-fat diet (HF; 60%) or moderately high-fat diet (MHF;32%). Both conditions show an increase of microglial marker Iba-1 and a decrease in the number of ORNs in the OM due to apoptosis (Thiebaud et al, 2014;Fardone et al, 2019). The consequence of the reduced number of ORN is a decreased number of axonal projections to the glomerulus.…”

“…At the level of the MOB, DIO has a clear structural impact. In transgenic mice carrying a GFP tag on the M72 odorant receptor, (Fardone et al, 2019) have described that in the medial but not the lateral glomerulus targeted by the M72 receptors, the number of juxta-glomerular cells is decreased in mild or HFD compared to control mice. The excitability of those cells is also impaired.…”

“…Overall, GLP-1R expressed in the olfactory system is a good candidate for pharmacological treatment to rescue olfaction in the context of obesity and T2D. Fardone et al, 2019;Lacroix et al, 2015;Rivière et al, 2016;Thiebaud et al, 2014Lietzau et al, 2018Fardone et al, 2019;Poessel et al, 2020aLietzau et al, 2018 Insulin resistance Fadool et al, 2004;Aimé et al, 2012;Tucker et al, 2012a;Lacroix et al, 2015;Min and Min, 2018;Poessel et al, 2020b Al Koborssy et al, 2019 Leptin resistance Getchell et al, 2006;Chelminski et al, Summary and chronology of the events related to food intake which directly or indirectly impact the olfactory system, and which may be altered in condition of T2D or obesity. GIT = gastro-intestinal tract; GLP-1 = Glucagon-like peptide-1; GIP = Gastric inhibitory polypeptide; CCK = Cholecystokinin.…”