Endocrine Abstracts

Background: Adipose tissue exhibits an altered adipokine secretion profile in obesity which is pro-inflammatory and relates to higher risk of cardio-metabolic diseases. Asprosin is a novel pleiotropic adipokine with orexigenic and glucogenic effects which is secreted in response to fasting. Elevated circulating asprosin levels have been shown in obesity and type 2 diabetes, as well as in other cardio-metabolic diseases. Furthermore, in vitro studies have reported pro-inflammatory effects of asprosin in various tissues. Previously, we have shown that asprosin acts partly via the NFkB pathway to induce an acute pro-inflammatory response in THP-1 macrophages. The present study aimed to investigate the in vitro effects of a Toll-like receptor 4 (TLR4)-specific signalling inhibitor (TAK-242) on THP-1 macrophages.

Methods: THP-1 monocytes were differentiated to macrophages by 48-hour treatment with 100 nM Dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL LPS and 1µM TAK-242. The expression and secretion of pro-inflammatory mediators were measured by qPCR, western blot, ELISA and Bioplex.

Results: Asprosin stimulation significantly upregulates the expression and secretion of pro-inflammatory cytokines; TNFα, IL1β, IL8, and IL12. Furthermore, a 15-minute asprosin stimulation increased the phosphorylation of AMPK, JNK and NFkB. Pre-treatment with TAK-242 significantly inhibited gene expression and release of key pro-inflammatory cytokines, including TNFα (P=0.0028 and P=0.023, respectively), IL1β (P=0.0004 and P=0.021, respectively) and IL8 (P=0.0012 and P=0.0126, respectively). Furthermore, TAK-242 treatment significantly inhibited MCP1 secretion (P=0.0001) in THP1 macrophages.

Conclusion: Asprosin induces a pro-inflammatory response in macrophages which is significantly inhibited by a TLR4-specific signalling inhibitor. Although further studies are still required to identify the complete signalling pathways involved, the present findings suggest that the asprosin-induced pro-inflammatory effects are partly mediated through the TLR4 signalling pathway.