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

Park O, Ki SH, Xu M, Wang H, Feng D, Tam J, Osei-Hyiaman D, Kunos G, Gao B - Cell Biosci (2015)

Bottom Line: These inhibitory effects were partially reversed by blocking STAT3 or the AMPK signaling pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Liver Diseases, NIAAA/NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.

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.

No MeSH data available.


Related in: MedlinePlus

Chronic administration of rmIL-22 protein does not affect body weight and insulin resistance in HFD-fed mice. Mice were fed a HFD for 5 months and then injected with rmIL-22 (20 ng/g body weight, i.p. injection, twice a week) or saline for an additional four weeks. a Body weights were measured. b Fasting blood glucose levels. Values represent the mean ± SEM (n = 8)
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Fig4: Chronic administration of rmIL-22 protein does not affect body weight and insulin resistance in HFD-fed mice. Mice were fed a HFD for 5 months and then injected with rmIL-22 (20 ng/g body weight, i.p. injection, twice a week) or saline for an additional four weeks. a Body weights were measured. b Fasting blood glucose levels. Values represent the mean ± SEM (n = 8)

Mentions: To further clarify this discrepancy, we treated HFD-fed mice with rmIL-22 (R&D system) (20 ng/g body weight, twice a week) for 4 weeks. Our results revealed that such treatment did not affect body weight and fasting glucose levels (Fig. 4a-b) and insulin and glucose intolerance (data not shown).Fig. 4


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

Park O, Ki SH, Xu M, Wang H, Feng D, Tam J, Osei-Hyiaman D, Kunos G, Gao B - Cell Biosci (2015)

Chronic administration of rmIL-22 protein does not affect body weight and insulin resistance in HFD-fed mice. Mice were fed a HFD for 5 months and then injected with rmIL-22 (20 ng/g body weight, i.p. injection, twice a week) or saline for an additional four weeks. a Body weights were measured. b Fasting blood glucose levels. Values represent the mean ± SEM (n = 8)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4462081&req=5

Fig4: Chronic administration of rmIL-22 protein does not affect body weight and insulin resistance in HFD-fed mice. Mice were fed a HFD for 5 months and then injected with rmIL-22 (20 ng/g body weight, i.p. injection, twice a week) or saline for an additional four weeks. a Body weights were measured. b Fasting blood glucose levels. Values represent the mean ± SEM (n = 8)
Mentions: To further clarify this discrepancy, we treated HFD-fed mice with rmIL-22 (R&D system) (20 ng/g body weight, twice a week) for 4 weeks. Our results revealed that such treatment did not affect body weight and fasting glucose levels (Fig. 4a-b) and insulin and glucose intolerance (data not shown).Fig. 4

Bottom Line: These inhibitory effects were partially reversed by blocking STAT3 or the AMPK signaling pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Liver Diseases, NIAAA/NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.

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.

No MeSH data available.


Related in: MedlinePlus