Endocrine Abstracts

Introduction: Asprosin is a novel adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes mellitus. In vitro studies have reported pro-inflammatory effects of asprosin in pancreatic β-cells and skeletal muscle cells, which appear to be mediated via a toll-like receptor 4 (TLR4) mediated pathway, and may contribute to the metabolic dysregulation observed in such diseases. The aim of the present study was to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages.

Methods: Differentiated THP-1 macrophages were treated with either 1, 10, 100 nM asprosin, 100 ng/mL LPS or both 100 nM asprosin and 100 ng/mL LPS for 4 and 24 hours. Caffeic acid phenethyl ester (CAPE; 10 μM) was used as an inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB). Cell and supernatant samples were collected and analysed by luminometry, flow cytometry, RT-qPCR and ELISA.

Results: Asprosin promoted gene expression and release of key pro-inflammatory cytokines, including TNFα (P = 0.044 and P = 0.0006, respectively), IL-1β (P < 0.0001 and P = 0.0084, respectively) and IL-8 (P = 0.021 and P < 0.0001, respectively), after 4 hours of treatment, which subsided by 24 hours. Asprosin-stimulated secretion of TNFα from THP-1 macrophages was significantly decreased with the addition of CAPE after 4 hours of treatment (P = 0.033). Although asprosin did not induce superoxide release, it significantly attenuated LPS-induced superoxide release from THP-1 macrophages (P = 0.0071). Asprosin did not significantly affect the cell surface expression of TLR4 in THP-1 macrophages.

Conclusions: The present study demonstrates that asprosin acts partly via the NFkB pathway to induce an acute pro-inflammatory response in THP-1 macrophages. Further studies are required to elucidate the involvement of additional signalling pathways in these pro-inflammatory effects.