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Neuroinflammatory responses following zinc or branched-chain amino acids supplementation in obese rats

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Abstract

The excessive production of pro-inflammatory mediators, characteristic of obesity, leads to neuroinflammation. Zinc (Zn) and the branched-chain amino acids (BCAA) are supplements known for their immunomodulatory properties. Our goal was to evaluate if Zn or BCAA supplementation can affect long-term recognition memory and neuroinflammatory parameters of obese rats after a high-fat diet (HFD). Three-month-old Wistar rats were divided into six groups: Standard diet (SD) + vehicle; SD + Zn; SD + BCAA; High-fat diet (HFD) + vehicle; HFD + Zn; and HFD + BCAA. Diets were administrated for 19 weeks, Zn (1,2 mg/kg/day) or BCAA (750 mg/kg/day) supplementation was conducted in the last 4 weeks. Long-term recognition memory was evaluated by the novel object recognition test. IL-1β immunoreactivity in the cortex and hippocampus, and IL-6 levels in the cortex tissue were assessed. Astrogliosis were evaluated through GFAP + cell count and morphological analysis (Sholl Method). Zn supplementation improved object recognition memory in HFD-fed rats, which was not observed following BCAA supplementation. The levels of IL-6 in the cerebral cortex were higher after HFD, which was not diminished after neither supplementation. Obesity also led to increased IL-1β immunoreactivity in the cerebral cortex and hippocampus, which was reduced by Zn. BCAA supplementation also diminished IL-1β immunoreactivity, but only in the hippocampus. We also showed that astrocyte reactivity caused by HFD is area-dependent, being the cerebral cortex more susceptible to the diet. Even though BCAA and Zn can affect IL-1β immunoreactivity and astrocyte morphology, only Zn improved memory. Future studies are needed to clarify the pathways by which Zn improves cognition in obesity.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Brazilian funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS); G.S. Feijó and J. Jantsch were recipients of FAPERGS and CNPq fellowships, respectivelly. L.L. Correia and S.Eller were recipients of UFCSPA fellowships.

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Authors and Affiliations

  1. Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245, Porto Alegre, Brazil

    Grace dos Santos Feijó, Jeferson Jantsch, Orlando Vieira Furtado-Filho, Márcia Giovenardi, Marilene Porawski, Elizandra Braganhol & Renata Padilha Guedes

  2. Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, 90050-170, Brazil

    Lidia Luz Correia

  3. Programa de Pós-Graduação Em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245, Porto Alegre, Brazil

    Sarah Eller

  4. Programa de Pós-Graduação Em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite 245, 308 C, Porto Alegre, RS, 90050-170, Brazil

    Márcia Giovenardi, Elizandra Braganhol & Renata Padilha Guedes

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  1. Grace dos Santos Feijó
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  2. Jeferson Jantsch
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  3. Lidia Luz Correia
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  4. Sarah Eller
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  6. Márcia Giovenardi
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  7. Marilene Porawski
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  8. Elizandra Braganhol
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  9. Renata Padilha Guedes
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Contributions

Renata Padilha Guedes and Marilene Porawski conceived the presented idea. Grace dos Santos Feijó, Jeferson Jantsch, Lidia Luz Correia, Sarah Eller, and Orlando Vieira Furtado Filho carried out the experiments. Grace dos Santos Feijó, Renata Padilha Guedes, Elizandra Braganhol and Márcia Giovenardi contributed to the interpretation of the results. Grace dos Santos Feijó and Jeferson Jantsch wrote the manuscript in consultation with Renata Padilha Guedes and Elizandra Braganhol. All authors read and approved the final manuscript.

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Correspondence to Renata Padilha Guedes.

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All procedures were approved by the Institutional Animal Care and Use Committee (UFCSPA, Brazil, protocol No. 359/16).

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Feijó, G.d., Jantsch, J., Correia, L.L. et al. Neuroinflammatory responses following zinc or branched-chain amino acids supplementation in obese rats. Metab Brain Dis 37, 1875–1886 (2022). https://doi.org/10.1007/s11011-022-00996-5

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