Superiority of the Non-Glycosylated Form over the Glycosylated Form of Irisin in the Attenuation of Adipocytic Meta-Inflammation: A Potential Factor in the Fight against Insulin Resistance

摘要

Irisin is an adipomyokine that promotes the browning of white adipose tissue and exhibits protective potential against the development of insulin resistance and type 2 diabetes. In our bodies, it occurs in its glycosylated form (G-IR): its activity is still poorly understood, because the majority of studies have used its non-glycosylated counterpart (nG-IR). Glycosylation can affect protein function: therefore, the present study attempted to compare the actions of both forms of irisin toward inflammatory activation of the main component of adipose tissue. The study was carried out in a coculture of 3T3 adipocytes and RAW 264.7 macrophages maintained in the presence of nG-IR or G-IR. The impact on vitality and the expression and release of key inflammatory mediators important for insulin resistance and diabetes development were assessed. The studies showed that both forms effectively inhibited the expression and release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, macrophage chemotactic protein (MCP)-1, high-mobility group box (HMGB1), leptin, and adiponectin. However, in the case of TNF-α, IL-1β, MCP-1, and HMGB1, the inhibition exerted by nG-IR was more prominent than that by G-IR. In addition, only nG-IR significantly inhibited macrophage migration. Here, nG-IR seemed to be the stronger inhibitor of the development of obesity-related inflammation; however, G-IR also had anti-inflammatory potential.