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Effects of a Novel Magnesium Complex on Metabolic and Cognitive Functions and the Expression of Synapse-Associated Proteins in Rats Fed a High-Fat Diet

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Abstract

This study was conducted to compare the effects of a novel form of magnesium, Mg picolinate (MgPic), to magnesium oxide (MgO) on metabolic and cognitive functions and the expression of genes associated with these functions in rats fed a high-fat diet (HFD). Forty-two Wistar rats were divided into six groups: control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was supplemented at 500 mg of elemental Mg/kg diet for 8 weeks. MgPic and MgO supplementation decreased visceral fat, serum glucose, insulin, leptin, TC, TG, FFA, testosterone, FSH, LH, SHBG, IGF-1, and MDA levels, but increased brain SOD, CAT, and GSH-Px activities in HFD rats. Inflammation and cognitive-related markers (presynaptic synapsin PSD95, postsynaptic PSD93, postsynaptic GluR1, and GluR2) were improved in HFD rats administered Mg, with more significant effects seen in the MgPic group. MgPic also decreased brain NF-κB but elevated brain Nrf2 levels, compared with the HFD group. The phosphorylation levels of Akt (Thr308), Akt (Ser473), PI3K try 458/199, and Ser9-GSK-3 in the brain were improved after Mg treatment in HFD rats, with more potent effects seen from MgPic supplementation. MgPic has a higher bioavailability and is more effective in improving metabolic parameters and enhancing memory than MgO. The pro-cognitive effects of MgO and MgPic could be mediated via modulation of the AMPA-type glutamate receptor and activation of the PI3K-Akt–GSK-3β signaling pathway. These findings further support the use of MgPic in the management of metabolic and cognitive disorders.

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Funding

This study received funding from Nutrition 21 LLC (Purchase, NY, USA) and the Turkish Academy of Sciences (in part, K.S.). The funders were not involved in the study design, collection, analysis, and interpretation of data; the writing of this article; or the decision to submit it for publication.

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Authors and Affiliations

  1. Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, 23119, Elazig, Turkey

    Cemal Orhan, Nurhan Sahin & Kazim Sahin

  2. Department of Biology, Faculty of Science, Firat University, 23119, Elazig, Turkey

    Mehmet Tuzcu

  3. Department of Animal Biology, Faculty of Science, University of Dschang, Dschang, Cameroon

    Patrick Brice Deeh Defo

  4. Scientific and Regulatory Affairs, Nutrition 21 LLC, Purchase, NY, USA

    Sara Perez Ojalvo, Sarah Sylla & James R. Komorowski

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Contributions

1) K.S. and C.O. were involved in the conception and design and edited and reviewed the main manuscript text. C.O., M.T., and N.S. performed the experiments and analyzed the data. P.B.D.D., S.S., and S.P.O. drafted the manuscript; J.R.K. revised and edited the manuscript. All authors have read and agreed to the published version of the manuscript. All authors agree to be accountable for all aspects of the work.

2) All authors confirm that our figures/tables are original and have not been published previously.

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Correspondence to Kazim Sahin.

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The study was approved by the Animal Ethics Committee of Firat University (156-2017/86) and performed following the internationally accepted standard ethical guidelines for laboratory animal use and care as described in the European Community guidelines, EEC Directive 2010/63/EU, of the 22 September 2010.

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All authors confirm that our figures/tables are original and have not been published previously.

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SPO, SS, and JRK are an employee of Nutrition 21, LLC, and New York, USA. Other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

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Orhan, C., Tuzcu, M., Deeh Defo, P.B. et al. Effects of a Novel Magnesium Complex on Metabolic and Cognitive Functions and the Expression of Synapse-Associated Proteins in Rats Fed a High-Fat Diet. Biol Trace Elem Res 200, 247–260 (2022). https://doi.org/10.1007/s12011-021-02619-z

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