Trace Element Homeostasis Research Articles

Associations Between Mild Cognitive Impairment and Whole Blood Zinc and Selenium in the Elderly Cohort.

Some studies have shown that an imbalance in trace element homeostasis can lead to cognitive dysfunction, but data are lacking. The purpose of this study was to investigate the association between whole blood zinc (Zn), selenium (Se), copper-zinc ratio (Cu/Zn), copper-selenium ratio (Cu/Se), and zinc-selenium ratio (Zn/Se) and mild cognitive impairment (MCI) in elderly Chinese individuals. The study was based on the Elderly Health and Controlled Environmental Factors Cohort in Lu'an, Anhui Province, China, from June to September 2016. The cognitive function of the elderly was determined by the Mini-Mental State Examination (MMSE) and activities of daily living (ADL) scales. The concentrations of Zn, Cu, and Se in the whole blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Binary logistic regression was used to analyze the associations between trace elements and MCI. A total of 1006 participants with an average age of 71.70years old were included in this study. Compared with healthy people, MCI patients had higher whole blood Zn levels and lower Se levels, and Cu/Zn, Cu/Se, and Zn/Se were also significantly different. Binary logistic regression analysis showed that Zn, Cu/Se, and Zn/Se exposure in the third tertile was associated with an increased risk of MCI, while Se exposure in the third tertile was associated with a reduced risk of MCI. After adjustment for sex, age, marital status, BMI, and living status, whole blood Zn, Se, Cu/Zn, Cu/Se, and Zn/Se were significantly associated with MCI risk, especially in elderly women.

Selenium protects against cadmium-induced cardiac injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling.

Cadmium (Cd) is an environmental pollutant that has an enormous influence on agricultural production, but selenium (Se) can alleviate its toxicity. The present study aimed to illustrate the effects of Se on Cd-induced heart injury. All 40 rabbits were randomly divided into four groups: control group, Se [0.5mg kg-1 ·body weight (BW)] group, Cd (1mg kg-1 ·BW) group, and Se + Cd group. After 30 days of feeding, morphological changes, the levels of oxidative stress and myocardial enzyme, the content of cardiac troponin T, programmed cell death (pyroptosis, autophagy and apoptosis), and PI3K/AKT/PTEN transduction capacity were observed. The results showed that Cd destroyed the physiological balance of trace elements and caused myocardial damage, increased the cardiac oxidative damage and led to programmed cell death. Coadministration of Se prominently ameliorated histological lesions and improved cardiac function of hearts in Cd-induced rabbits. Furthermore, Se exerted detoxification and oxidation resistance, maintained trace element homeostasis, and alleviated the changes of mRNA and protein levels of pyroptosis-, autophagy- and apoptosis-controlling factors and PI3K/AKT/PTEN signal molecules caused by Cd. In conclusion, Se might protect against Cd-induced pyroptosis, autophagy and apoptosis by interfering with PI3K/AKT/PTEN signaling in heart.

Dietary Trace Element Intake and Risk of Breast Cancer: A Mini Review.

Trace elements are essentially required for various physiological and metabolic functions, and any disturbance in the trace elements homeostasis may result in the development of chronic diseases including breast cancer. Breast cancer is the most prevalent cancer type reported in women equally affecting both the high-income and low-income countries. This review therefore aimed to evaluate the impact of dietary trace element intake in relation to the incidence of breast cancer. We focused on five trace elements, thus emphasizing dietary selenium, zinc, iron, copper, and cadmium intake and risk of breast cancer. A systematic approach was applied to perform this review through entering a search term in PubMed and Scopus databases. A total of 24 articles were included after meeting the inclusion and exclusion criteria. Most of the studies regarding dietary iron intake showed a detrimental effect of increased dietary heme iron on breast cancer incidence risk. In addition, there is a limited evidence of high dietary intake of selenium and zinc to reduce the risk of breast cancer. Also, a few studies showed a relationship between high cadmium consumption and risk of breast cancer. More studies related to cadmium and copper exposure are needed to confirm this relationship. As a result, the findings of this review suggested that high dietary heme iron is a potential risk factor for breast cancer.

High glucose induced inflammation is inhibited by copper chelation via rescuing mitochondrial fusion protein 2 in retinal pigment epithelial cells

Altered trace element homeostasis is associated with diabetic complications, and studies have shown elevated copper levels in the serum of individuals with type 1 & 2 diabetes. Copper chelation has been shown to be beneficial by preventing or reversing diabetic organ damage and developing as a new treatment strategy for treating diabetic complications. Diabetic retinopathy is the major vision-threatening complication of diabetes. Recent studies have reported copper to be elevated in the serum of patients with diabetic retinopathy. Here in this study, we attempt to unravel the role of copper chelator penicillamine in retinal pigment epithelial cells exposed to high glucose (HG) and copper as a model for diabetic retinopathy. We have found that high glucose by itself and along with copper alters the mitochondrial morphology, reduces the expression of the mitochondrial fusion protein 2 (MFN2), and induces endoplasmic reticulum (ER) stress and inflammation. Copper chelation with penicillamine reduced all these changes in mitochondria, thereby rescuing the cells from mitochondrial damage and inflammation.

ВЛИЯНИЕ ПОГОДНЫХ ФАКТОРОВ НА ЭЛЕКТРОЛИТНУЮ И МИКРОЭЛЕМЕНТНУЮ ХРОНОПЕРИОДИЧЕСКУЮ СИСТЕМУ У БОЛЬНЫХ ИБС / INFLUENCE OF WEATHER FACTORS ON ELECTROLYTES AND MICROELEMENTS CHRONOPERIODICAL SYSTEM IN PATIENTS WITH ISCHEMIC HEART DISEASE

Изучены адаптационные особенности водно-минеральной хронопериодической системы у здоровых лиц и больных ИБС. / Seventy practically healthy subjects and 110 patients with ischemic heart disease were unified regimen of diet, sleep and wakefulness. Urine was collected with 4-h portions during 3–5 days. Each specimen was analyzed for electrolytes (sodium, potassium, phosphorus, chlorine, calcium, magnesium) and trace elements (iron, copper, zinc, chromium, cadmium, vanadium). Rhythms parameters have been estimated by dispersion analysis for nonsinusoidal rhythms and by nonlinear least squares method for sinusoidal rhythms. In healthy individuals acrophases of electrolytes and trace elements homeostasis were outstripping the acrophases of the rhythms of meteorological factors. In patients with ischemic heart disease acrophases of biorhythms often were concurrent or delayed relative of the acrophases of the rhythms of weather indices.

Characteristics of immune hormonal and trace element homeostasis in overweight male adolescents and its diagnostic value

Characteristics of immune hormonal and trace element homeostasis in overweight male adolescents and its diagnostic value

Drosophila melanogaster as a Model Organism to Study Lithium and Boron Bioactivity.

The fruit fly Drosophila melanogaster has become a valuable model organism in nutritional science, which can be applied to elucidate the physiology and the biological function of nutrients, including trace elements. Importantly, the application of chemically defined diets enables the supply of trace elements for nutritional studies under highly standardized dietary conditions. Thus, the bioavailability and bioactivity of trace elements can be systematically monitored in D. melanogaster. Numerous studies have already revealed that central aspects of trace element homeostasis are evolutionary conserved among the fruit fly and mammalian species. While there is sufficient evidence of vital functions of boron (B) in plants, there is also evidence regarding its bioactivity in animals and humans. Lithium (Li) is well known for its role in the therapy of bipolar disorder. Furthermore, recent findings suggest beneficial effects of Li regarding neuroprotection as well as healthy ageing and longevity in D. melanogaster. However, no specific essential function in the animal kingdom has been found for either of the two elements so far. Here, we summarize the current knowledge of Li and B bioactivity in D. melanogaster in the context of health and disease prevention.

The retention of Zr from potential therapeutic silica-zirconia core–shell nanoparticles in aquatic organisms

Model experiments under laboratory conditions were carried out to assess the accumulation tendency of Zr from a silica-zirconia core–shell nanoparticles, synthesised for the assay. Acute exposition tests were conducted with Daphnia magna and Danio rerio and the accumulation tendency of the nano and the molecular form was compared. Significant elevation of Zr was found in the tissue of the test organisms treated by the NP compared to the control, however, the retention of zebrafish was lower than that of the daphnids. Increased level of bioconcentration factor and the strong correlation of the redundancy analysis data suggest accumulation tendency in D. magna, yet long-term experiments are required to prove and further assess the environmental risk of food-chain bioconcentration. The BCF results were under the REACH limit for the D. rerio groups indicating the low short-term accumulation tendency of Zr from the NP. However, Zr level was significantly higher in zebrafish individuals originating from the SiO2@ZrO2 NP exposed treatments compared to the groups supplemented by the same concentration of ZrOCl2, which did not result in the elevation of Zr in fish tissue. The trace element homeostasis of D. rerio was not affected by the acute SiO2@ZrO2 NP exposition and no lethality occurred.

In vivo assessment of molybdenum and cadmium co-induce nephrotoxicity via NLRP3/Caspase-1-mediated pyroptosis in ducks

Excessive molybdenum (Mo) and cadmium (Cd) cause toxic effects on animals, but their joint effects on pyroptosis in kidney of ducks remain unclear. 160 healthy 7-day-old ducks were randomly divided into four groups which were fed with basal diet containing different dosages of Mo or/and Cd for 16 weeks. On the 4th, 8th, 12th and 16th weeks, kidney tissue and serum were collected. The results showed that Mo or/and Cd could significantly elevate their contents in kidney, disturb the homeostasis of trace elements, cause renal function impairment and histological abnormality, and oxidative stress as accompanied by increasing hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations and decreasing glutathione peroxidase (GSH-Px), catalase (CAT) and total-superoxide dismutase (T-SOD) activities. Simultaneously, Mo or/and Cd could markedly increase interleukin-1β (IL-1β), interleukin-18 (IL-18) contents and the expression levels of pyroptosis-related genes (NOD-like receptor protein-3 (NLRP3), Caspase-1, apoptosis-associated speck-like protein (ASC), NIMA-related kinase 7 (NEK7), Gasdermin A (GSDMA), Gasdermin E (GSDME), IL-1β and IL-18) and proteins (NLRP3, Caspase-1 p20, ASC and Gasdermin D (GSDMD)). Moreover, the changes of above these indicators were more obvious in combined group. Taken together, the results illustrate that Mo and Cd might synergistically lead to oxidative stress and induce pyroptosis via NLRP3/Caspase-1 pathway, whose mechanism is somehow related to Mo and Cd accumulation in duck kidneys.

Synchrotron-Based Imaging Reveals the Fate of Selenium in Striped Marsh Frog Tadpoles.

Synchrotron-based X-ray fluorescence microscopy (XFM) coupled with X-ray absorption near-edge structure (XANES) imaging was used to study selenium (Se) biodistribution and speciation in Limnodynastes peronii tadpoles. Tadpoles were exposed to dissolved Se (30 μg/L) as selenite (SeIV) or selenate (SeVI) for 7 days followed by 3 days of depuration. High-resolution elemental maps revealed that Se partitioned primarily in the eyes (specifically the eye lens, iris, and retinal pigmented epithelium), digestive and excretory organs of SeIV-exposed tadpoles. Speciation analysis confirmed that the majority of accumulated Se was converted to organo-Se. Multielement analyses provided new information on Se colocalization and its impact on trace element homeostasis. New insights into the fate of Se on a whole organism scale contribute to our understanding of the mechanisms and risks associated with Se pollution.

Advances in nutrient metabolism and emission of livestock and poultry dietary trace elements

<p indent=0mm>Trace elements, including iron, copper, manganese, zinc, selenium, and iodine, comprise less than 0.01% of animals, yet are essential nutrients and key factors in the plant-animal-soil cycle. Trace elements have important physiological functions and are often required for enzymatic reactions, energy metabolism, and synthesis of materials, immune defense, and other activities necessary for life. Micronutrient deficiency causes developmental disorders and decreased immunity in young animals, and even leads to nutritional metabolic diseases and death. Supplementation of the diet of livestock and poultry with trace elements is closely related to growth and reproductive performance. Many studies have demonstrated that dietary supplementation with trace elements improves production performance and the content of these elements in livestock and poultry products. Due to the low bioavailability of dietary trace elements, excess trace elements may be added to livestock and poultry diets. However, animals generally have self-regulatory mechanisms of absorption and metabolism to maintain the homeostasis of trace elements. Excess dietary trace elements that are not absorbed are discharged in the excrement and pollute farm soil and water sources. In particular, heavy metals, such as copper, zinc, manganese, chromium, and cadmium, detrimentally affect the growth of crops and change the composition and structure of soil microorganism. Human health can also be affected when heavy metals bioaccumulate through the food chain. Breeding and consumption of livestock and poultry occur on a large scale in China, the excrement from livestock and poultry is an important source of heavy metals in the environment. Soil, water, and crops in most areas of China are seriously affected by heavy metal pollution. Clarifying the nutrient metabolism and emission of dietary trace elements to reduce environmental con-tamination is crucial to improve the economic benefits of breeding, protect the ecological environment of breeding areas, and promote the healthy and sustainable development of the breeding industry. In recent years, increasing attention has focused on reducing environmental pollution caused by heavy metals from livestock and poultry, while maintaining the efficiency of breeding production. Appropriate reductions of trace elements in livestock and poultry diets do not impact growth performance and reduce the content of trace elements in excreta. In addition, organic trace element additives demonstrate higher bioavailability with less emission. This article summarizes the nutritional function, absorption and metabolism mechanism, enrichment characteristics of livestock and poultry products, and fecal excretion patterns of trace elements. The appropriate lower levels, improved dosage form of supplemented dietary trace elements, and a model of combined planting and breeding may alleviate trace element pollution in livestock and poultry breeding.

The Disturbance of Anticancer Drug Cisplatin to Cellular Homeostasis of Trace Elements Revealed by ICP-MS and ToF-SIMS

The Disturbance of Anticancer Drug Cisplatin to Cellular Homeostasis of Trace Elements Revealed by ICP-MS and ToF-SIMS

Patterns and Associations of Essential Trace Elements (Cu, Fe and Zn) in Saudi Adults with Varying Levels of Glycemia.

The homeostasis of trace elements were observed to contribute to certain diabetic outcomes. This cross-sectional study determined the differences and associations between serum levels of copper (Cu), iron (Fe) and zinc (Zn) in Saudi patients with and without type 2 diabetes mellitus (T2DM) as well as those with prediabetes. Anthropometrics were measured, and fasting blood samples were collected from 119 patients with T2DM (aged 41–64 years), 95 non-T2DM (aged 27–55 years) and 80 with prediabetes (aged 35–57 years). Circulating trace minerals were determined using an inductively coupled plasma–mass spectrometer. Serum levels of Cu and Fe were significantly lower in T2DM than non-T2DM (adjusted p-values < 0.001). There was no difference in the Zn levels of the T2DM and non-T2DM groups. The serum Cu levels were significantly lower in the prediabetes group than the non-T2DM group (p < 0.05). The serum levels of Cu, Fe and Zn were inversely associated with circulating glucose in the T2DM and prediabetes subjects (p-values < 0.001). In conclusion, the differences in circulating trace elements were observed in Saudi subjects with varying glycemic statuses, suggesting an inverse association between T2DM progression and the decreasing serum Cu, Fe and Zn levels. Intervention trials are warranted to determine whether early correction of trace mineral deficiencies is beneficial in populations at higher risk for T2DM.

РОЛЬ МИКРОЭЛЕМЕНТОВ В ТЕЧЕНИИ БЕРЕМЕННОСТИ

Trace elements take part in the implementation of the most important metabolic processes of the body. Violation of trace element homeostasis during pregnancy leads to the formation of various pathologies. Deficiency of zinc, manganese, selenium and cobalt, high or low copper content in the blood of a pregnant woman increases the risk of developing preeclampsia, anemia and miscarriages. А low boron content is observed with gestational diabetes mellitus and chronic arterial hypertension in pregnant women. Cobalt deficiency is associated with an increased risk of premature birth, the development of iron deficiency anemia, and arterial hypertension during gestation. A sufficient amount of molybdenum is necessary for the onset of pregnancy, its lack leads to a change in carbohydrate metabolism, the formation of xanthine stones, the occurrence of nausea, anemia and caries in pregnant women. Nickel deficiency leads to the development of iron deficiency anemia and impairment of reproductive function, and its excess can contribute to the formation of gestational diabetes mellitus. The addition of trivalent chromium to the diet of women with polycystic ovary syndrome increases the likelihood of pregnancy, and an excess of its hexavalent form positively correlates with the risk of developing preeclampsia and premature rupture of membranes. The increased consumption of Ni, Cr6+ and F has an adverse effect on the health of the pregnant woman. To fully understand the role of trace elements in ensuring maternal health and the proper development of the fetus, further studies of their concentrations and control values in amniotic fluid, maternal serum and umbilical cord blood during pregnancy are needed to determine the optimal level of supplementation and to quickly diagnose maternal and embryonic mineral metabolic disorders.

Biomonitorization of concentrations of 28 elements in serum and urine among workers exposed to indium compounds.

Many studies have documented the abnormal concentrations of metals/metalloids in serum or urine of occupational workers, but no works systematically analysed the concentrations of elements in serum or urine of indium-exposed workers. This study was aimed to assess 28 elements in serum and urine from 57 individuals with occupational exposure to indium and its compounds. Control subjects were 63 workers without metal exposure. We collected information on occupation and lifestyle habits by questionnaire. Biological samples were collected to quantify elements by inductive coupled plasma-mass spectrometer. Air in the breathing zones was drawn at flow rates of 1.5-3 L/min for a sampling period of 6 to 8 h, using a Model BFC-35 pump. The average ambient indium level was 0.078 mg/m3. Serum/urine Indium levels were significantly higher in indium-exposed workers than in controls (P < 0.01). Moreover, serum/urine indium concentrations in the group with 6-14 years and ≥15 years of employment were significantly higher than those with ≤5 employment years(P < 0.05). Ten of the other 27 elements/metals measured were higher in serum/urine in indium-exposed workers compared to the controls (aluminum, beryllium, cadmium, cesium, chromium, lithium, manganese, magnesium, molybdenum and vanadium). Zinc levels in serum/urine were significantly decreased in the indium-exposed workers. Additionally, other elements/metals were higher in one specimen (serum or urine) but lower in the other (Selenium was lower in serum but higher in urine in the indium-exposed workers compared with the controls; likewise Thallium and Rubidium were higher in serum but lower in urine). Linear regression analyses, revealed significant correlations between serum and urine for indium, aluminum, arsenic, barium, cadmium, cesium, cobalt, selenium, silver, and zinc (P < 0.05). These data suggest that occupational exposure to indium and its compounds may disturb the homeostasis of trace elements in systemic circulation, indium concentrations in serum or urine appear reflective of workers' exposure to ambient indium and their years of working, respectively. The serum/urine levels of essential metals are modified by exposure to indium in occupationally exposed workers. Further studies including larger sample size and more kinds of biological sample are needed to validate our findings.

Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers

BackgroundBeing an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer’s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. MethodsIn this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. ResultsCopper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 μM) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. ConclusionOne potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.

Toward unzipping the ZIP metal transporters: structure, evolution, and implications on drug discovery against cancer

The Zrt-/Irt-like protein (ZIP) family consists of divalent metal transporters, ubiquitous in all kingdoms of life. Since the discovery of the first ZIPs in the 1990s, the ZIP family has been expanding to contain tens of thousands of members playing key roles in uptake and homeostasis of life-essential trace elements, primarily zinc, iron and manganese. Some family members are also responsible for toxic metal (particularly cadmium) absorption and distribution. Their central roles in trace element biology, and implications in many human diseases, including cancers, have elicited interest across multiple disciplines for potential applications in biomedicine, agriculture and environmental protection. In this review and perspective, selected areas under rapid progress in the last several years, including structural biology, evolution, and drug discovery against cancers, are summarised and commented. Future research to address the most prominent issues associated with transport and regulation mechanisms are also discussed.

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

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.

N-Acetylcysteine as Modulator of the Essential Trace Elements Copper and Zinc.

N-acetylcysteine (NAC) is a frequently prescribed drug and known for its metal chelating capability. However, to date it is not well characterized whether NAC intake affects the homeostasis of essential trace elements. As a precursor of glutathione (GSH), NAC also has the potential to modulate the cellular redox homeostasis. Thus, we aimed to analyze effects of acute and chronic NAC treatment on the homeostasis of copper (Cu) and zinc (Zn) and on the activity of the redox-sensitive transcription factor Nrf2. Cells were exposed to 1 mM NAC and were co-treated with 50 μM Cu or Zn. We showed that NAC treatment reduced the cellular concentration of Zn and Cu. In addition, NAC inhibited the Zn-induced Nrf2 activation and limited the concomitant upregulation of cellular GSH concentrations. In contrast, mice chronically received NAC via drinking water (1 g NAC/100 mL). Cu and Zn concentrations were decreased in liver and spleen. In the duodenum, NQO1, TXNRD, and SOD activities were upregulated by NAC. All of them can be induced by Nrf2, thus indicating a putative Nrf2 activation. Overall, NAC modulates the homeostasis of Cu and Zn both in vitro and in vivo and accordingly affects the cellular redox balance.

The influence of sex and strain on trace element dysregulation in the brain due to diet-induced obesity

BackgroundThe objective of this study was to identify interaction effects between diet, sex, and strain on trace element dysregulation and gene expression alterations due to diet-induced obesity (DIO) in the hippocampus, striatum, and midbrain. MethodsMale and female C57BL/6 J (B6 J) and DBA/2 J (D2 J) mice were fed either a low fat (10 % kcal) diet (LFD) or high fat (60 % kcal) diet (HFD) for 16 weeks, then assessed for trace element concentrations and gene expression patterns in the brain. ResultsIn the hippocampus, zinc was significantly increased by 48 % in D2 J males but decreased by 44 % in D2 J females, and divalent metal transporter 1 was substantially upregulated in B6 J males due to DIO. In the striatum, iron was significantly elevated in B6 J female mice, and ceruloplasmin was significantly upregulated in D2 J female mice due to DIO. In the midbrain, D2 J males fed a HFD had a 48 % reduction in Cu compared to the LFD group, and D2 J females had a 37 % reduction in Cu compared to the control group. ConclusionsThe alteration of trace element homeostasis and gene expression due to DIO was brain-region dependent and was highly influenced by sex and strain. A significant three-way interaction between diet, sex, and strain was discovered for zinc in the hippocampus (for mice fed a HFD, zinc increased in male D2 Js, decreased in female D2 Js, and had no effect in B6 J mice). A significant diet by sex interaction was observed for iron in the striatum (iron increased only in female mice fed a HFD). A main effect of decreased copper in the midbrain was found for the D2 J strain fed a HFD. These results emphasize the importance of considering sex and genetics as biological factors when investigating potential associations between DIO and neurodegenerative disease.