The GLP-1 receptor agonist Liraglutide attenuates intermittent hypoxia-induced pro-inflammatory macrophage polarization in primary macrophages

Abstract

<b>Background:</b> Intermittent hypoxia (IH)-induced pro-inflammatory M1-macrophage polarization likely plays a key role in the pathogenesis of metabolic perturbations in obstructive sleep apnoea (OSA). We have recently shown using primary macrophages that this response is mediated through the TLR4/NFκB pathway¹ and thus, this pathway may represent a potential therapeutic target. Recent evidence suggested attenuation of pro-inflammatory response in macrophages by the glucagon-like peptide-1 receptor (GLP-1R) agonist, Liraglutide. Here, we tested the hypothesis that Liraglutide protects against IH-induced responses using our state-of-the-art <i>in-vitro</i> model of IH. <b>Methods:</b> Bone marrow-derived macrophages isolated from C56BL/6 male mice were exposed to IH or intermittent normoxia as previously described¹ in the presence or absence of 250nM Liraglutide. RNA was extracted and analysed via RT-qPCR for expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and iNOS. <b>Results:</b> As expected, IH resulted in increased mRNA expression of the potent pro-inflammatory macrophage markers iNOS, IL-1β and IL-6, in comparison to normoxic controls. Liraglutide significantly attenuated the IH-mediated increase in IL-1β (0.5±0.42 fold over control, p=0.031) and iNOS (0.14±0.18 fold over control, p=0.001) and there was a trend towards reduced expression in IL-6. <b>Conclusion:</b> Liraglutide attenuates IH-induced pro-inflammatory responses in primary macrophages. Further experiments <i>in-vitro</i> and <i>in-vivo</i> will determine the role of this intervention in metabolic diseases in OSA. ¹Fitzpatrick SF et al, J Sleep Res: e13202