New insight into the direct anti-inflammatory activity of a myokine irisin against proinflammatory activation of adipocytes. Implication for exercise in obesity.

A biological activity of myokine irisin, has been intensively investigated in the context of a browning process occurring in white adipose tissue, but its role as a modulator of immune response has been little studied. The aim of our study was to determine the impact of irisin (0 - 100 nM) on pro-inflammatory activation of adipocyte 3T3 L1 cell line. Irisin reduced in a concentration-dependent manner the expression and activity of major proinflammatory cytokines, e.g. tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) expression and their secretion into cell medium. Moreover, irisin enhanced adiponectin synthesis reversing the effect of the lipopolysaccharide (LPS)-induced attenuation of this adipokine expression. The opposite effect was observed for leptin whose expression increased by LPS and this effect was suppressed by irisin application. A decreased phosphorylation and activation of nuclear factor kappa B (NFκB) in the presence of irisin suggests that mechanism of action irisin involves the inhibition of an inflammatory transcription factor. Irisin exerts also an inhibitory effect on macrophage migration toward chemoattractants present in adipocyte supernatants. Among the specific molecules secreted by adipocytes was monocyte chemotactic protein 1 (MCP-1) whose expression was suppressed by irisn. In majority of experiments irisin was effective in 100 nM concentration but in some of them the inhibitory effects occurred already in a concentration of 50 nM of this peptide. This study for the first time showed that adipocytes are directly affected by irisin and provides an evidence on anti-inflammatory action of irisin on fat cells.