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Lactate Production can Function to Increase Human Epithelial Cell Iron Concentration.

Caroline Ghio1, Joleen M Soukup2, Lisa A Dailey2

  • 1Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 313 Snell Engineering, Boston, MA 02115 USA.

Cellular and Molecular Bioengineering
|December 19, 2022
PubMed
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Lactate enhances iron import in human epithelial cells. Lactate dehydrogenase (LDH) activity and blood LDH levels correlate with iron availability and homeostasis, suggesting a role for lactate in iron metabolism.

Area of Science:

  • Biochemistry
  • Human Physiology
  • Cell Biology

Background:

  • Limited iron availability triggers metabolic adaptations in plants and microbes for iron acquisition.
  • Carboxylates and hydroxycarboxylates act as ligands to solubilize and facilitate iron uptake.
  • Human intestinal epithelial cells may produce lactate during iron deficiency to enhance iron import.

Purpose of the Study:

  • To investigate if lactate increases iron import in epithelial cells in vitro.
  • To determine if lactate dehydrogenase (LDH) activity and lactate production correlate with iron availability.
  • To examine the correlation between blood LDH concentrations and iron homeostasis indices in humans.

Main Methods:

  • Exposure of Caco-2 cells to sodium lactate and ferric ammonium citrate (FAC) to assess iron import.
Keywords:
Carboxylic acidsCoordination complexesIronLactate dehydrogenasesLactates

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  • Measurement of LDH activity and lactate levels in epithelial cells under varying iron conditions.
  • Analysis of National Health and Nutrition Examination Survey data for correlations between blood LDH and serum iron.

    • Main Results:

    • Sodium lactate and other carboxylates increased iron import in Caco-2 cells when combined with FAC.
    • Increased iron import led to elevated ferritin and mitochondrial iron.
    • LDH activity decreased with FAC exposure, and blood LDH showed a negative correlation with serum iron in human cohorts.

    Conclusions:

    • Lactate plays a role in iron import by human epithelial cells.
    • LDH activity serves as a potential indicator of cellular iron availability.
    • Blood LDH concentrations correlate with systemic iron homeostasis.