# Dihydroxyacetone exposure induces metabolic reprogramming and mitochondrial dysfunction

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2021 · $346,500

## Abstract

Each puff of an e-cigarette generates micromolar amounts dihydroxyacetone (DHA) from the combustion of
propylene glycol and glycerol. Up to 40-55% of e-liquid content is converted to DHA in each puff from an e-
cigarette, making DHA a high-volume component found in all e-cigarette vapors, which the vaper inhales with
each puff of the e-cigarette. DHA is approved for external use as a sunless tanning agent, but serious
concerns have been raised about inhalation exposures through spray tanning and now e-cigarette use. We
have shown that DHA is genotoxic, cytotoxic, and induces mitochondrial dysfunction in skin and kidney cells,
but the effects of inhalation exposures to DHA are currently unknown. The long-term goal of the proposal is the
identification and validation of markers for cellular and metabolic stress induced by DHA exposure that can be
examined in tissues from vapers to understand the consequences of repeated inhalation exposures to DHA.
The objective of this proposal is to address the gap in existing studies, which have only focused on skin
models, by examining the exposure effects of DHA at both acute and chronic doses in pulmonary and
cardiovascular cells. Our central hypothesis is that exposure to DHA alters metabolic pathways, promotes
oxidative stress, disrupts Ca2+ homeostasis, and leads to mitochondrial dysfunction. The rationale for this
work is that DHA exposures to the lung and cardiovascular system allow direct absorption of DHA into cells.
DHA-induced changes in metabolism and mitochondrial function would compromise overall cellular function,
leading to disease. Three specific aims will test the central hypothesis: 1) DHA incorporation into metabolic
pathways alters glycolysis and induces glycosylation protein damage; 2) DHA exposure alters NAD(P)H pools
inducing oxidative stress, and 3) DHA exposure alters cytosolic Ca2+ levels and disrupts mitochondrial
function. The first aim will test the sub-hypothesis that DHA alters metabolic pathways by tracing DHA
metabolism using isotopologues of DHA and identifying metabolite disequilibrium. The second aim will test the
sub-hypothesis that an excess of DHA changes cofactor pools and induces oxidative stress. The third aim will
test the sub-hypothesis that DHA alters Ca2+ signaling to induce mitochondrial dysfunction, in addition to
causing metabolic stress and oxidation-reduction imbalance. The study is innovative because it extends
beyond the genotoxic and cytotoxic characterization of DHA to measure DHA’s ability to reprogram pulmonary
and cardiovascular cells metabolically. The research is significant because e-cigarette users are chronically
exposed to DHA, which will directly impact pulmonary and cardiovascular cell homeostasis and cause severe
declines in cellular function or even induce cell death. This work will establish essential markers for DHA
exposure to allow future epidemiological work to associate DHA exposure to disease.

## Key facts

- **NIH application ID:** 10097623
- **Project number:** 1R01ES032450-01
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Natalie Rose Gassman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,500
- **Award type:** 1
- **Project period:** 2021-01-01 → 2021-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10097623

## Citation

> US National Institutes of Health, RePORTER application 10097623, Dihydroxyacetone exposure induces metabolic reprogramming and mitochondrial dysfunction (1R01ES032450-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10097623. Licensed CC0.

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