IL-29 promoted obesity-induced inflammation and insulin resistance

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity.Interleukin-29(IL-29),a member of type 3 interferon family,plays a role in host defenses against microbes,however,little is known about its role in metabolic disorders.We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance.We found that serum IL-29 level was significantly higher in obese patients.IL-29 upregulated IL-1β,IL-8,and monocyte chemoattractant protein-1(MCP-1)expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome(SGBS)adipocytes through reducing glucose transporter 4(GLUT4)and AKT signals.In addition,IL-29 promoted monocyte/macrophage migration.Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system,which mimic an obese microenvironment.In vivo,IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet(HFD)-induced obese mice.IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice.Therefore,we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance,and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.