Diet-Induced Obesity Disrupts Trace Element Homeostasis and Gene Expression in the Olfactory Bulb

Abstract

The aim of this study was to determine the impact of diet-induced obesity (DIO) on trace element homeostasis and gene expression in the olfactory bulb and to identify potential interaction effects between diet, sex, and strain. Our study is based on evidence that obesity and olfactory bulb impairments are linked to neurodegenerative processes. Briefly, C57BL/6J (B6J) and DBA/2J (D2J) male and female mice were fed either a low-fat diet or a high-fat diet for 16 weeks. Brain tissue was then evaluated for iron, manganese, copper, and zinc concentrations and mRNA gene expression. There was a statistically significant diet-by-sex interaction for iron and a three-way interaction between diet, sex, and strain for zinc in the olfactory bulb. Obese male B6J mice had a striking 75% increase in iron and a 50% increase in manganese compared with the control. There was an increase in zinc due to DIO in B6J males and D2J females, but a decrease in zinc in B6J females and D2J males. Obese male D2J mice had significantly upregulated mRNA gene expression for divalent metal transporter 1, alpha-synuclein, amyloid precursor protein, dopamine receptor D2, and tyrosine hydroxylase. B6J females with DIO had significantly upregulated brain-derived neurotrophic factor expression. Our results demonstrate that DIO has the potential to disrupt trace element homeostasis and mRNA gene expression in the olfactory bulb, with effects that depend on sex and genetics. We found that DIO led to alterations in iron and manganese predominantly in male B6J mice, and gene expression dysregulation mainly in male D2J mice. These results have important implications for health outcomes related to obesity with possible connections to neurodegenerative disease.

Effect of Probiotic Lacticaseibacillus rhamnosus LB1.5 on Anxiety-like Behavior, Neuroprotection and Neuroinflammation Markers of Male Mice Fed a High-Fat Diet

“…Despite the impact of HFD on obesity and associated metabolic disorders being well-documented in the literature [ 28 , 29 , 30 ], the effects of probiotic Lact. rhamnosus LB1.5 supplementation on these parameters remains relatively understudied.…”

Aqueous Extract of Psiloxylon mauritianum, Rich in Gallic Acid, Prevents Obesity and Associated Deleterious Effects in Zebrafish

“…Under overweight and obesity conditions, brain homeostasis is impaired in both mammals and zebrafish [ 29 , 54 , 81 ]. We and others have previously demonstrated that DIO disrupts brain homeostasis by inducing BBB breakdown, cerebral oxidative stress and neuro-inflammation associated with impaired neurogenesis [ 29 , 39 , 40 , 53 , 54 , 82 , 83 ].…”

Sexually dimorphic metal alterations in childhood obesity are modulated by a complex interplay between inflammation, insulin, and sex hormones

“…11 Other authors have demonstrated that diet-induced obesity disrupts trace element homeostasis in various brain regions of mice in a sexspecific manner. 18,19 Furthermore, there is increasing evidence suggesting that adverse health effects triggered by the exposure to toxic heavy metals (e.g., cadmium, lead) may differ depending on sex, which could be attributed to differences in kinetics, mode of action, or susceptibility. 20 In this work, we studied the influence of sex in modulating metal metabolism in childhood obesity and IR.…”

“…However, Błażewicz et al interestingly found that the sex criterion may influence the association between metal contents and the BMI of children (e.g., negative correlation between BMI and blood Zn, plasma Cu, and urinary Fe among girls; positive correlation between BMI and plasma Co among boys) 11 . Other authors have demonstrated that diet‐induced obesity disrupts trace element homeostasis in various brain regions of mice in a sex‐specific manner 18,19 . Furthermore, there is increasing evidence suggesting that adverse health effects triggered by the exposure to toxic heavy metals (e.g., cadmium, lead) may differ depending on sex, which could be attributed to differences in kinetics, mode of action, or susceptibility 20 …”