Abstract
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.
Highlights
Obesity is considered as a serious global epidemic that significantly affects population health.[1,2,3] According to the statistics of WHO in 2014, more than 600 million adults were obese in the world and it is further projected that 1.12 billion individuals will be classified as obese by 2030.4,5 The main cause is due to the imbalance between intake and consumption of calories, so that excessive energy stored in adipocytes leads to increase of cell numbers and expansion of cell size
Several studies have identified that the production of IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) were elevated in obesity, which impaired insulin signaling indicating that inflammation is critical in the pathogenesis of obesity-induced metabolic disorders.[13,14,15,16,17]
IL-29 is expressed in human adipose tissue and higher serum IL-29 levels were detected in obese patients
Summary
Obesity is considered as a serious global epidemic that significantly affects population health.[1,2,3] According to the statistics of WHO in 2014, more than 600 million adults were obese in the world and it is further projected that 1.12 billion individuals will be classified as obese by 2030.4,5 The main cause is due to the imbalance between intake and consumption of calories, so that excessive energy stored in adipocytes leads to increase of cell numbers (hyperplasic adipocytes) and expansion of cell size (hypertrophic adipocytes). Obesity elevates the morbidity of cardiovascular disease, type 2 diabetes mellitus (T2DM), degenerative arthritis, and nonalcoholic fatty liver disease compared with healthy people.[6,7]. Hypertrophied adipocytes and adipose tissue-resident immune cells (primarily lymphocytes and macrophages) both contribute to higher proinflammatory cytokine production in the obese. Several studies have identified that the production of IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) were elevated in obesity, which impaired insulin signaling indicating that inflammation is critical in the pathogenesis of obesity-induced metabolic disorders.[13,14,15,16,17]
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