Palmitate exacerbates bisphenol A toxicity via induction of ER stress and mitochondrial dysfunction

Anupom Mondal, Natalie Burchat, Harini Sampath

Research output: Contribution to journalArticlepeer-review

Abstract

Combined exposure to dietary nutrients and environmental chemicals may elicit significantly different physiological effects than single exposures. Exposure to dietary saturated fats and environmental toxins is a physiologically-significant dual exposure that is particularly associated with lower socioeconomic status, potentially placing these individuals at heightened risk of xenobiotic toxicities. However, no prior studies have examined interactions between specific lipids and environmental xenobiotics in modulating cellular health. Using primary mouse embryonic fibroblasts, we have discovered that prior exposure to the saturated fatty acid, palmitate, exacerbates cellular toxicity associated with the industrial plasticizer, bisphenol A (BPA). Cell death upon BPA exposure following palmitate pre-treatment was greater than that occurring with either exposure alone. Mechanistically, cell death was preceded by increased endoplasmic reticulum stress and loss of mitochondrial membrane potential in palmitate plus BPA exposed cells, leading to increased caspase-3 cleavage and subsequent apoptosis. Interestingly, inclusion of the unsaturated fatty acid, oleate, along with palmitate during the pre-treatment period completely abrogated the ER stress, mitochondrial toxicity, and cell death induced by subsequent exposure to BPA. Thus, our data identify for the first time an important interaction between a fatty acid and an environmental toxin and have implications for developing nutritional interventions to mitigate the deleterious effects of such xenobiotic exposures.

Original languageEnglish (US)
Article number158816
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1866
Issue number1
DOIs
StatePublished - Jan 2021
Externally publishedYes

Keywords

  • Bisphenol A
  • ER stress
  • Mitochondrial dysfunction
  • Oleate
  • Palmitate
  • Saturated fat

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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