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Park O, Ki SH, Xu M, et al. Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences. Cell Biosci. 2015;5:25doi: 10.1186/s13578-015-0015-0.
Park, O., Ki, S. H., Xu, M., Wang, H., Feng, D., Tam, J., Osei-Hyiaman, D., Kunos, G., & Gao, B. (2015). Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences. Cell & bioscience, 525. https://doi.org/10.1186/s13578-015-0015-0
Park, Ogyi, et al. "Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences." Cell & bioscience vol. 5 (2015): 25. doi: https://doi.org/10.1186/s13578-015-0015-0
Park O, Ki SH, Xu M, Wang H, Feng D, Tam J, Osei-Hyiaman D, Kunos G, Gao B. Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences. Cell Biosci. 2015 May 30;5:25. doi: 10.1186/s13578-015-0015-0. eCollection 2015. PMID: 26064446; PMCID: PMC4462081.
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Cell Biosci. 2015 May 30;5:25. doi: 10.1186/s13578-015-0015-0. eCollection 2015.

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

Cell & bioscience

Ogyi Park, Sung Hwan Ki, Mingjiang Xu, Hua Wang, Dechun Feng, Joseph Tam, Douglas Osei-Hyiaman, George Kunos, Bin Gao

Affiliations

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

PMID: 26064446 PMCID: PMC4462081 DOI: 10.1186/s13578-015-0015-0

Abstract

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.

Keywords: Cytokine; Hyperglycemia; Insulin resistance; Liver; Obesity

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