Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences

Cell & Bioscience

Bin Gao⁴  George Kunos¹  Douglas Osei-Hyiaman¹  Joseph Tam²  Dechun Feng⁴  Hua Wang⁴  Mingjiang Xu⁴  Sung Hwan Ki³  Ogyi Park⁴ 

[1] Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda 20892, MD, USA;Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel;Laboratory of Toxicology, College of Pharmacy, Chosun University, Gwangju, South Korea;Laboratory of Liver Diseases, NIAAA/NIH, 5625 Fishers Lane, Bethesda 20892, MD, USA

关键词: Liver;    Cytokine;    Hyperglycemia;    Insulin resistance;    Obesity;   

Others  :  1224960
DOI  :  10.1186/s13578-015-0015-0

 received in 2015-03-24, accepted in 2015-05-14,  发布年份 2015

【 摘 要 】

Background

Interleukin-22 (IL-22), a cytokine with important functions in anti-microbial defense and tissue repair, has been recently suggested to have beneficial effects in obesity and metabolic syndrome in some but not in other studies. Here, we re-examined the effects of IL-22 on obesity, insulin resistance, and hepatic glucose metabolism.

Results

Genetic deletion of IL-22 did not affect high-fat-diet (HFD)-induced obesity and insulin resistance. IL-22 transgenic mice with relatively high levels of circulating IL-22 (~600 pg/ml) were completely resistant to Concanavalin A-induced liver injury but developed the same degree of high fat diet (HFD)-induced obesity, insulin resistance, and fatty liver as the wild-type littermate controls. Similarly, chronic treatment with recombinant mouse IL-22 (rmIL-22) protein did not affect HFD-induced obesity and the associated metabolic syndrome. In vivo treatment with a single dose of rmIL-22 downregulated the hepatic expression of gluconeogenic genes and subsequently inhibited hepatic gluconeogenesis and reduced blood glucose levels both in HFD-fed and streptozotocin (STZ)-treated mice without affecting insulin production. In vitro exposure of mouse primary hepatocytes to IL-22 suppressed glucose production and the expression of gluconeogenic genes. These inhibitory effects were partially reversed by blocking STAT3 or the AMPK signaling pathway.

Conclusion

Biologically active, high levels of IL-22 do not affect obesity and the associated metabolic syndrome. Acute treatment with IL-22 inhibits hepatic gluconeogenesis, which is mediated via the activation of STAT3 and AMPK in hepatocytes.

【 授权许可】

   
2015 Park et al.; licensee BioMed Central.

【 图 表 】

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