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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

Endogenous IL-22 does not play a role in the development of obesity and insulin resistance induced by a HFD. a Two-month old IL-22TG6 mice and their littermate controls were fed a HFD or CD for 10 weeks. Serum IL-22 levels were measured. b, c Two-month old IL-22KO mice and their littermate controls were fed a HFD or CD for 10 weeks. Body weight was counted weekly (panel b); GTT and ITT were examined after 10 weeks feeding (panel c). CD; control diet; HFD: high-fat diet. Values represent the mean ± SEM (n = 6-12)
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Fig1: Endogenous IL-22 does not play a role in the development of obesity and insulin resistance induced by a HFD. a Two-month old IL-22TG6 mice and their littermate controls were fed a HFD or CD for 10 weeks. Serum IL-22 levels were measured. b, c Two-month old IL-22KO mice and their littermate controls were fed a HFD or CD for 10 weeks. Body weight was counted weekly (panel b); GTT and ITT were examined after 10 weeks feeding (panel c). CD; control diet; HFD: high-fat diet. Values represent the mean ± SEM (n = 6-12)

Mentions: It was reported that basal serum levels of IL-22 were approximately 20 pg/ml in control diet-fed mice, and were decreased to 5 pg/ml in HFD-fed mice [28]. However, a recent study reported that serum levels of IL-22 were markedly increased after HFD diet feeding to approximately 1000 pg/ml compared to approximately 100 pg/ml in chow-fed mice (Extended data Fig. 1 in reference [19]). Here we found that serum IL-22 levels were relatively low (<20 pg/ml) in control- or HFD-fed mice with lower levels in HFD-fed mice than those in control-fed mice, while high levels of serum IL-22 were detected in IL-22TG6 mice (~600 pg/ml) (Fig. 1a). HFD feeding did not affect serum IL-22 levels in IL-22TG6 mice.Fig. 1


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)

Endogenous IL-22 does not play a role in the development of obesity and insulin resistance induced by a HFD. a Two-month old IL-22TG6 mice and their littermate controls were fed a HFD or CD for 10 weeks. Serum IL-22 levels were measured. b, c Two-month old IL-22KO mice and their littermate controls were fed a HFD or CD for 10 weeks. Body weight was counted weekly (panel b); GTT and ITT were examined after 10 weeks feeding (panel c). CD; control diet; HFD: high-fat diet. Values represent the mean ± SEM (n = 6-12)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Endogenous IL-22 does not play a role in the development of obesity and insulin resistance induced by a HFD. a Two-month old IL-22TG6 mice and their littermate controls were fed a HFD or CD for 10 weeks. Serum IL-22 levels were measured. b, c Two-month old IL-22KO mice and their littermate controls were fed a HFD or CD for 10 weeks. Body weight was counted weekly (panel b); GTT and ITT were examined after 10 weeks feeding (panel c). CD; control diet; HFD: high-fat diet. Values represent the mean ± SEM (n = 6-12)
Mentions: It was reported that basal serum levels of IL-22 were approximately 20 pg/ml in control diet-fed mice, and were decreased to 5 pg/ml in HFD-fed mice [28]. However, a recent study reported that serum levels of IL-22 were markedly increased after HFD diet feeding to approximately 1000 pg/ml compared to approximately 100 pg/ml in chow-fed mice (Extended data Fig. 1 in reference [19]). Here we found that serum IL-22 levels were relatively low (<20 pg/ml) in control- or HFD-fed mice with lower levels in HFD-fed mice than those in control-fed mice, while high levels of serum IL-22 were detected in IL-22TG6 mice (~600 pg/ml) (Fig. 1a). HFD feeding did not affect serum IL-22 levels in IL-22TG6 mice.Fig. 1

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