TY - JOUR
T1 - Palmitate exacerbates bisphenol A toxicity via induction of ER stress and mitochondrial dysfunction
AU - Mondal, Anupom
AU - Burchat, Natalie
AU - Sampath, Harini
N1 - Funding Information:
We thank the lab of Dr. Tracy Anthony (Rutgers University) for generously providing ER stress-related antibodies and primers, and Dr. Sai Komakula (Sampath Lab, Rutgers University) for technical assistance with MEF isolations and Seahorse assays. This work was supported by NIH grant DK100640 and AHA grant 20CDA35310305 , both to H.S.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Bisphenol A
KW - ER stress
KW - Mitochondrial dysfunction
KW - Oleate
KW - Palmitate
KW - Saturated fat
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U2 - 10.1016/j.bbalip.2020.158816
DO - 10.1016/j.bbalip.2020.158816
M3 - Article
C2 - 32976987
AN - SCOPUS:85091756315
VL - 1866
JO - BBA - Specialised Section On Lipids and Related Subjects
JF - BBA - Specialised Section On Lipids and Related Subjects
SN - 1388-1981
IS - 1
M1 - 158816
ER -