Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice: Trace Element Status, Genomic Stability, Inflammation, and Epigenetics

Mol Nutr Food Res. 2020 Aug;64(16):e2000325. doi: 10.1002/mnfr.202000325. Epub 2020 Jul 16.

Abstract

Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied.

Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass-spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron-related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation.

Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects.

Keywords: DNA (hydroxy)methylation; genomic stability; health parameters of mice; trace element biomarkers; trace element interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein
  • DNA Methylation / drug effects
  • DNA Methylation / physiology
  • Epigenesis, Genetic
  • Feces / chemistry
  • Ferritins / blood
  • Genomic Instability / drug effects*
  • Genomic Instability / physiology
  • Glutathione Peroxidase / blood
  • Glutathione Peroxidase / metabolism
  • Inflammation / immunology
  • Interleukin-6 / blood
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / blood
  • Tissue Distribution
  • Trace Elements / analysis*
  • Trace Elements / pharmacology*
  • Transferrin / analysis
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Interleukin-6
  • Nerve Tissue Proteins
  • Trace Elements
  • Transferrin
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • neuronal pentraxin
  • C-Reactive Protein
  • Ferritins
  • Glutathione Peroxidase