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

Abstract

Background: 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 in-vitro model of IH.

Methods: 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.

Results: 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.

Conclusion: Liraglutide attenuates IH-induced pro-inflammatory responses in primary macrophages. Further experiments in-vitro and in-vivo will determine the role of this intervention in metabolic diseases in OSA.

¹Fitzpatrick SF et al, J Sleep Res: e13202