Effects of ethanol or ethylene glycol exposure on PPARγ and aromatase expression in adipose tissue
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Effects of ethanol or ethylene glycol exposure on PPARγ and aromatase expression in adipose tissue. / Ardenkjær-Skinnerup, Jacob; Saar, Daniel; Christiansen, Sofie; Svingen, Terje; Hadrup, Niels; Brown, Kristy A.; Emanuelli, Brice; Kragelund, Birthe B.; Ravn-Haren, Gitte; Vogel, Ulla.
In: Biochemistry and Biophysics Reports, Vol. 38, 101742, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of ethanol or ethylene glycol exposure on PPARγ and aromatase expression in adipose tissue
AU - Ardenkjær-Skinnerup, Jacob
AU - Saar, Daniel
AU - Christiansen, Sofie
AU - Svingen, Terje
AU - Hadrup, Niels
AU - Brown, Kristy A.
AU - Emanuelli, Brice
AU - Kragelund, Birthe B.
AU - Ravn-Haren, Gitte
AU - Vogel, Ulla
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - The estrogen-synthesizing enzyme aromatase is expressed in adipose tissue where it controls the local concentration of estrogen. It has been suggested that the organic solvents ethanol and ethylene glycol can induce estrogen synthesis by inhibiting PPARγ activity. Since elevated estrogen synthesis in adipose tissue is a risk factor for breast cancer development, it is of interest to further characterize the mechanisms regulating aromatase expression. Here, we explored the mechanisms by which ethanol and ethylene glycol modulate aromatase mRNA expression and the ultimate conversion of androgens into estrogens. NMR spectroscopy revealed that ethanol and ethylene glycol influence the active state of PPARγ. An inhibitory effect on PPARγ was confirmed by adipogenesis assays and PPARγ target gene expression analysis in adipocytes. However, only ethanol increased aromatase mRNA in differentiated human adipocytes. In contrast, ethylene glycol downregulated aromatase in a PPARγ-independent manner. An animal study using female Wistar rats was conducted to assess the acute effects of ethanol and ethylene glycol on aromatase expression in adipose tissue within a physiological context. No changes in aromatase or PPARγ target gene (Adipoq and Fabp4) levels were observed in adipose tissue or ovary in response to the chemical exposures, suggesting an absence of acute PPARγ-mediated effects in these organs. The results suggest that ethanol and ethylene glycol are weak PPARγ antagonists in mouse and human adipocytes as well as in cell-free NMR spectroscopy. Both compounds seem to affect adipocyte aromatase expression in vitro, where ethanol increased aromatase expression PPARγ-dependently and ethylene glycol decreased aromatase expression independently of PPARγ. No acute effects on aromatase expression or PPARγ activity were observed in adipose tissue or ovary in rats in this study design.
AB - The estrogen-synthesizing enzyme aromatase is expressed in adipose tissue where it controls the local concentration of estrogen. It has been suggested that the organic solvents ethanol and ethylene glycol can induce estrogen synthesis by inhibiting PPARγ activity. Since elevated estrogen synthesis in adipose tissue is a risk factor for breast cancer development, it is of interest to further characterize the mechanisms regulating aromatase expression. Here, we explored the mechanisms by which ethanol and ethylene glycol modulate aromatase mRNA expression and the ultimate conversion of androgens into estrogens. NMR spectroscopy revealed that ethanol and ethylene glycol influence the active state of PPARγ. An inhibitory effect on PPARγ was confirmed by adipogenesis assays and PPARγ target gene expression analysis in adipocytes. However, only ethanol increased aromatase mRNA in differentiated human adipocytes. In contrast, ethylene glycol downregulated aromatase in a PPARγ-independent manner. An animal study using female Wistar rats was conducted to assess the acute effects of ethanol and ethylene glycol on aromatase expression in adipose tissue within a physiological context. No changes in aromatase or PPARγ target gene (Adipoq and Fabp4) levels were observed in adipose tissue or ovary in response to the chemical exposures, suggesting an absence of acute PPARγ-mediated effects in these organs. The results suggest that ethanol and ethylene glycol are weak PPARγ antagonists in mouse and human adipocytes as well as in cell-free NMR spectroscopy. Both compounds seem to affect adipocyte aromatase expression in vitro, where ethanol increased aromatase expression PPARγ-dependently and ethylene glycol decreased aromatase expression independently of PPARγ. No acute effects on aromatase expression or PPARγ activity were observed in adipose tissue or ovary in rats in this study design.
KW - Adipogenesis
KW - Adipose tissue
KW - Alcohol
KW - Aromatase
KW - Breast cancer
KW - PPARγ
U2 - 10.1016/j.bbrep.2024.101742
DO - 10.1016/j.bbrep.2024.101742
M3 - Journal article
AN - SCOPUS:85194430085
VL - 38
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
SN - 2405-5808
M1 - 101742
ER -
ID: 393842851