Exogenous exposure to dihydroxyacetone mimics high fructose induced oxidative stress and mitochondrial dysfunction

Environ Mol Mutagen. 2021 Mar;62(3):185-202. doi: 10.1002/em.22425. Epub 2021 Feb 6.

Abstract

Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette) combustion. Increased use of sunless tanning products and e-cigarettes has elevated exposures to DHA through inhalation and absorption. Studies have confirmed that DHA is rapidly absorbed into cells and can enter into metabolic pathways following phosphorylation to dihydroxyacetone phosphate (DHAP), a product of fructose metabolism. Recent reports have suggested metabolic imbalance and cellular stress results from DHA exposures. However, the impact of elevated exposure to DHA on human health is currently under-investigated. We propose that exogenous exposures to DHA increase DHAP levels in cells and mimic fructose exposures to produce oxidative stress, mitochondrial dysfunction, and gene and protein expression changes. Here, we review cell line and animal model exposures to fructose to highlight similarities in the effects produced by exogenous exposures to DHA. Given the long-term health consequences of fructose exposure, this review emphasizes the pressing need to further examine DHA exposures from sunless tanning products and e-cigarettes.

Keywords: dihydroxyacetone; fructose; glucose; inflammation; metabolic dysfunction; mitochondria; mitochondrial DNA; reactive oxygen species; reactive species.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Dihydroxyacetone / metabolism
  • Dihydroxyacetone / toxicity*
  • Dihydroxyacetone Phosphate / metabolism*
  • Fructose / toxicity
  • Humans
  • Metabolic Networks and Pathways / genetics
  • Mitochondria / drug effects
  • Mitochondria / genetics*
  • Mitochondria / pathology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Phosphorylation

Substances

  • Fructose
  • Dihydroxyacetone Phosphate
  • Dihydroxyacetone