GPER and ERα mediate estradiol enhancement of mitochondrial function in inflamed adipocytes through a PKA dependent mechanism

Abstract

Please cite this article as: Bauzá-Thorbrügge M, Rodríguez-Cuenca S, Vidal-Puig A, Galmés-Pascual BM, Sbert-Roig M, Gianotti M, Lladó I, Proenza AM, GPER and ER␣ mediate estradiol enhancement of mitochondrial function in inflamed adipocytes through a PKA dependent mechanism, Journal of Steroid Biochemistry and Molecular Biology (2018), https://doi.

Media composition and O2 levels determine effects of 17β-estradiol and selective estrogen receptor modulators on mitochondrial bioenergetics and cellular reactive oxygen species

“…2014;Sbert-Roig et al, 2016;Galmes-Pascual et al, 2017;Bauzá-Thorbrügge et al, 2019). This effect was observed here, as increases in mitochondrial footprint, under most experimental conditions.…”

G protein‐coupled oestrogen receptor stimulation ameliorates iron‐ and ovariectomy‐induced memory impairments through the cAMP/PKA/CREB signalling pathway

“…Remarkably, iron treatment combined with ovariectomy prevented training‐induced increases in CREB phosphorylation, whereas G1 administered immediately after training was able to restore CREB phosphorylation in the iron‐OVX group, similar to the recovery of memory deficits in this group (Experiments 2 and 3). Although the stimulation of GPER has not been previously linked to the cAMP/PKA/CREB pathway in the CNS, a recent study demonstrated that PKA inhibition prevented the improving effects of G1 on mitochondrial function in adipocytes under inflammatory conditions . CREB is a transcription factor that, when phosphorylated, regulates the expression of genes critically involved in synaptic plasticity and long‐term memory consolidation .…”

“…or vehicle (Veh) was administered 15 min before training and G1 (10 μg kg -1 , s.c.) dissolved in sunflower seed oil (Veh) was administered immediately after training of OP or IA (n = 8-9 per group in OP and n = 8-10 per group in IA). A significant difference between Iron-OVX-Veh-G1 compared to Iron-OVX-Veh-Veh is indicated as (**P < .0001), as well as between Iron-OVX-Veh-G1 compared to Iron-OVX-H89-G1 ( ## P < .0001 or # P < .05) 49 CREB is a transcription factor that, when phosphorylated, regulates the expression of genes critically involved in synaptic plasticity and long-term memory consolidation. [50][51][52][53][54] We have previously demonstrated that acute administration of rolipram, an agent that enhances the cAMP/PKA/CREB signalling pathway via the inhibition of phosphodiesterase type 4 (an enzyme that catalyses hydrolysis of cAMP), improves iron-induced memory deficits in male rats.…”

Targeting the G protein-coupled estrogen receptor (GPER) in obesity and diabetes

“…Similarly, treatment of DIO mice with E2 increased lipid oxidation to reduce obesity ( D’Eon et al, 2005 ). Cell-based studies revealed that in 3T3-L1 adipocytes treated with IL6 to induce inflammation-mediated mitochondrial dysfunction, treatment with E2 or G-1 attenuated the adverse effects of inflammation on mitochondrial function through activation of protein kinase A by ER α and GPER, thereby increasing mitochondrial biogenesis and oxygen consumption ( Bauza-Thorbrugge et al, 2019 ). Interestingly, in another model of GPER KO mice, GPER-lacZ mice (mutant mouse that harbors a β -galactosidase (lacZ) reporter within the Gper locus, disrupting Gper expression), female but not male GPER KO mice exhibited increased lipid accumulation in the liver along with decreased circulating HDL levels compared to WT mice ( Meoli et al, 2014 ).…”