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The first animal studies showing that GLP-1 potentially had effects on the CV system was published in 2002, and the first study to show cardioprotection was in 2008 (102, 211), but it was not until the LEADER cardiovascular outcomes trial (CVOT) with liraglutide, published in 2016, that a reduction in CV risk with a GLP-1RA was documented (100)

Furthermore, EDCs may activate microglia, increasing pro-inflammatory cytokine production and astroglia-mediated oxidative stress, exacerbating neuroinflammation

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To infer whether the observed changes in transcriptional gene programmes indicative of reduced synaptic plasticity by GIPR antagonism and GLP-1R agonism in the DVC translate to altered signalling in the hypothalamus, we performed a cellcell communication analysis using the LIANA+ 49 implementation of the CellPhoneDB 50 algorithm, and the receptorligand database from NeuronChat 51 (Fig