GPER and ERα mediate estradiol enhancement of mitochondrial function in inflamed adipocytes through a PKA dependent mechanism.
Galmés-Pascual, Bel M
Proenza, Ana M
J Steroid Biochem Mol Biol
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Bauzá-Thorbrügge, M., Rodríguez-Cuenca, S., Vidal-Puig, A., Galmés-Pascual, B. M., Sbert-Roig, M., Gianotti, M., Lladó, I., & et al. (2019). GPER and ERα mediate estradiol enhancement of mitochondrial function in inflamed adipocytes through a PKA dependent mechanism.. J Steroid Biochem Mol Biol, 185 256-267. https://doi.org/10.1016/j.jsbmb.2018.09.013
Obesity is associated with inflammation, dysregulated adipokine secretion, and disrupted adipose tissue mitochondrial function. Estradiol (E2) has been previously reported to increase mitochondrial function and biogenesis in several cell lines, but neither the type of oestrogen receptor (ERα, ERβ and GPER) involved nor the mechanism whereby such effects are exerted have been fully described. Considering the anti-inflammatory activity of E2 as well as its effects in enhancing mitochondrial biogenesis, the aim of this study was to investigate the contribution of ERα, ERβ, and GPER signaling to the E2-mediated enhancement of adipocyte mitochondrial function in a pro-inflammatory situation. 3T3-L1 cells were treated for 24 h with ER agonists (PPT, DPN, and G1) and antagonists (MPP, PHTPP, and G15) in the presence or absence of interleukin 6 (IL6), as a pro-inflammatory stimulus. Inflammation, mitochondrial function and biogenesis markers were analyzed. To confirm the involvement of the PKA pathway, cells were treated with a GPER agonist, a PKA inhibitor, and IL6. Mitochondrial function markers were analyzed. Our results showed that activation of ERα and GPER, but not ERβ, was able to counteract the proinflammatory effects of IL6 treatment, as well as mitochondrial biogenesis and function indicators. Inhibition of PKA prevented the E2- and G1-associated increase in mitochondrial function markers. In conclusion E2 prevents IL6 induced inflammation in adipocytes and promotes mitochondrial function through the combined activation of both GPER and ERα. These findings expand our understanding of ER interactions under inflammatory conditions in female rodent white adipose tissue.
Cell Line, 3T3 Cells, Mitochondria, Adipocytes, Animals, Mice, Inbred C57BL, Mice, Rats, Rats, Wistar, Obesity, Inflammation, Estradiol, Cyclic AMP-Dependent Protein Kinases, Receptors, G-Protein-Coupled, Estrogen Receptor alpha, Estrogen Receptor beta, Interleukin-6, Female, Male
European Commission (223450)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/2)
Biotechnology and Biological Sciences Research Council (BB/J009865/1)
British Heart Foundation (None)
External DOI: https://doi.org/10.1016/j.jsbmb.2018.09.013
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286644