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A high fat diet potentiates neonatal iron overload-induced memory impairments in rats

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Abstract

Purpose

The present study aimed at evaluating possible synergistic effects between two risk factors for cognitive decline and neurodegenerative disorders, i.e. iron overload and exposure to a hypercaloric/hyperlipidic diet, on cognition, insulin resistance, and hippocampal GLUT1, GLUT3, Insr mRNA expression, and AKT phosporylation.

Methods

Male Wistar rats were treated with iron (30 mg/kg carbonyl iron) or vehicle (5% sorbitol in water) from 12 to 14th post-natal days. Iron-treated rats received a standard laboratory diet or a high fat diet from weaning to adulthood (9 months of age). Recognition and emotional memory, peripheral blood glucose and insulin levels were evaluated. Glucose transporters (GLUT 1 and GLUT3) and insulin signaling were analyzed in the hippocampus of rats.

Results

Both iron overload and exposure to a high fat diet induced memory deficits. Remarkably, the association of iron with the high fat diet induced more severe cognitive deficits. Iron overload in the neonatal period induced higher insulin levels associated with significantly higher HOMA-IR, an index of insulin resistance. Long-term exposure to a high fat diet resulted in higher fasting glucose levels. Iron treatment induced changes in Insr and GLUT1 expression in the hippocampus. At the level of intracellular signaling, both iron treatment and the high fat diet decreased AKT phosphorylation.

Conclusion

The combination of iron overload with exposure to a high fat diet only led to synergistic deleterious effect on emotional memory, while the effects induced by iron and by the high fat diet on AKT phosphorylation were comparable. These findings indicate that there is, at least to some extent, an additive effect of iron combined with the diet. Further studies investigating the mechanisms associated to deleterious effects on cognition and susceptibility for the development of age-associated neurodegenerative disorders are warranted.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

This work was supported by National Council for Scientific and Technological Development [CNPq; Grant numbers 403154/2021-9 and 305656/2019-8 to N.S.]; the National Institute of Science and Technology for Translational Medicine [INCT-TM—Grant number 465458/2014-9]; National Institute of Science and Technology for Brain Diseases, Excitotoxicity and Neuroprotection [INCT-EN—Grant number 465671/2014-4]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. M.R.B, E.B., and N.S are Research Career Awardees of the CNPq. The funding sources were not involved in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Neurobiology and Developmental Biology Laboratory, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

    Filipe Valvassori do Nascimento, Betânia Souza de Freitas, Maiara Priscila dos Passos, Luiza Kleverston, Cristophod de Souza dos Santos & Elke Bromberg

  2. Laboratory of Genomics and Molecular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

    Luiza Wilges Kist & Maurício Reis Bogo

  3. Excitotoxicity and Neuroprotection (INCT-EN), National Institute of Science and Technology for Brain Diseases, Porto Alegre, Brazil

    Luiza Wilges Kist & Maurício Reis Bogo

  4. National Institute of Science and Technology for Translational Medicine (INCT-TM), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasília, Brazil

    Elke Bromberg & Nadja Schröder

  5. Department of Physiology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil

    Nadja Schröder

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  1. Filipe Valvassori do Nascimento
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Contributions

FVN: conceptualization, methodology, investigation, writing—original draft. MPP: investigation. BSF: investigation, resources, project administration. LK: investigation. CSS: investigation. LWK: investigation, validation. MRB: conceptualization, methodology, validation, writing—review and editing, funding acquisition. EB: conceptualization, methodology, validation, writing—review and editing, supervision, funding acquisition. NS: conceptualization, methodology, validation, formal analysis, writing—original draft, writing—review and editing, supervision, project administration, funding acquisition.

Corresponding author

Correspondence to Nadja Schröder.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was approved by the Institutional Ethics Committee for the Use of Animals of the Pontifical Catholic University (CEUA, #9331) and all experimental procedures were performed in accordance with the Brazilian Guidelines for the Care and Use of Animals in Research and Teaching (DBCA, published by CONCEA, MCTI, Brazil).

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do Nascimento, F.V., de Freitas, B.S., dos Passos, M.P. et al. A high fat diet potentiates neonatal iron overload-induced memory impairments in rats. Eur J Nutr 63, 1163–1175 (2024). https://doi.org/10.1007/s00394-024-03333-x

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