IL-29 promoted obesity-induced inflammation and insulin resistance

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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.

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Acknowledgements

We are grateful to Professor Martin Wabitsch (University of Ulm, Germany) and Professor Peter Staeheli (Medical Center University of Freiburg, Germany) for kindly providing SGBS preadipocyte cell line and IL-28R1−/− mice, respectively. This work was supported by the Ministry of Science and Technology of Taiwan (MOST-106-2311-B-006-008-MY2 and MOST-108-2320-B-006-052).

Author information

Y.-H.H conceived and supervised the study. Y.-H.H, T.-Y.L and C.-J.C designed the experiments, interpreted the results, and generated the figures. C.-H.K and C.-H.W collected the clinical samples and analyzed the data. Y.-H.H and T.-Y.L wrote the manuscript. Y.-H.H, T.-Y.L, C.-J.C, F.-H.C, and Y.-C.S performed the experiments and analyzed the data. All authors discussed the data and commented on the manuscript before submission.

Correspondence to Yu-Hsiang Hsu.

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The authors declare no competing interests.

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Keywords

  • cytokine
  • insulin resistance
  • inflammation
  • obesity