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Glyceryl triacetate feeding in mice increases plasma acetate levels but has no anticonvulsant effects in acute electrical seizure models

  • Author Footnotes
    1 ORCID: 0000-0003-3697-1581.
    Weizhi Xu
    Footnotes
    1 ORCID: 0000-0003-3697-1581.
    Affiliations
    School of Biomedical Sciences, Skerman Building 65, The University of Queensland, St. Lucia, QLD 4072, Australia
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  • Author Footnotes
    2 ORCID: 0000-0002-1632-9615.
    Elliott S. Neal
    Footnotes
    2 ORCID: 0000-0002-1632-9615.
    Affiliations
    School of Biomedical Sciences, Skerman Building 65, The University of Queensland, St. Lucia, QLD 4072, Australia
    Search for articles by this author
  • Manuel Plan
    Affiliations
    Metabolomics Australia, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, QLD 4072, Australia
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  • Author Footnotes
    3 ORCID: 0000-0001-7448-0770.
    Karin Borges
    Correspondence
    Corresponding author.
    Footnotes
    3 ORCID: 0000-0001-7448-0770.
    Affiliations
    School of Biomedical Sciences, Skerman Building 65, The University of Queensland, St. Lucia, QLD 4072, Australia
    Search for articles by this author
  • Author Footnotes
    1 ORCID: 0000-0003-3697-1581.
    2 ORCID: 0000-0002-1632-9615.
    3 ORCID: 0000-0001-7448-0770.
Published:November 04, 2022DOI:https://doi.org/10.1016/j.yebeh.2022.108964

      Highlights

      • Glyceryl triacetate (GTA) diet increased plasma acetate and propionate levels.
      • Glyceryl triacetate had no anticonvulsant effects in two acute electrical seizure threshold models.
      • Glyceryl triacetate feeding did not alter body weights and hematological parameters.
      • Cerebral cortex acetyl-CoA synthetase activity was unchanged by the GTA diet.
      • Plasma and cerebral cortex antioxidant capacity were unaltered by the GTA diet.

      Abstract

      Introduction

      Acetate has been shown to have neuroprotective and anti-inflammatory effects. It is oxidized by astrocytes and can thus provide auxiliary energy to the brain in addition to glucose. Therefore, we hypothesized that it may protect against seizures, which is investigated here by feeding glyceryl triacetate (GTA), to provide high amounts of acetate without raising sodium or acid levels.

      Method

      CD1 male mice were fed controlled diets with or without GTA for up to three weeks. Body weights, blood glucose levels, plasma short-chain fatty acid levels, and other hematological parameters were monitored. Seizure thresholds were determined in 6 Hz and maximal electroshock seizure threshold (MEST) tests. Antioxidant capacities were evaluated in the cerebral cortex and plasma using a ferric reducing antioxidant power (FRAP) assay and Trolox equivalent antioxidant capacity assay.

      Results

      Body weight gain was similar with both diets with and without GTA in two experiments. Glyceryl triacetate-fed groups showed 2–3- and 1.6-fold increased acetate and propionate levels in plasma, respectively. Glucose levels were unaltered in blood collected from the tail tip but increased in trunk blood. No differences were found in the activity of cerebral cortex acetyl-CoA synthetase. In the 6 Hz threshold test, seizure thresholds were lower by 3 mA and 2.4 mA after 8 and 14 days, respectively, in the GTA compared to the control diet-fed group, but showed no difference on day 16, showing that GTA has small, but inconsistent proconvulsant effects in this model. In MEST tests, a slightly increased seizure threshold (1 mA) was found on day 19 in the GTA-fed group, but not in another experiment on day 21. There were no differences in antioxidant capacity in plasma or cortex between the two groups.

      Conclusion

      Glyceryl triacetate feeding showed no antioxidant effects nor beneficial changes in acute electrical seizure threshold mouse models, despite its ability to increase plasma acetate levels.

      Keywords

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