IL-37 protects against obesity-induced inflammation and insulin resistance

Dov B. Ballak; Janna A. Van Diepen; Alexander R. Moschen; Henry J. Jansen; Anneke Hijmans; Gert-jan Groenhof; Floris Leenders; Philip Bufler; Mark V. Boekschoten; Michael Müller; Sander Kersten; Suzhao Li; Soohyun Kim; Hadar Eini; Eli C. Lewis; Leo A. B. Joosten; Herbert Tilg; Mihai G. Netea; Cees J. Tack; Charles A. Dinarello; Rinke Stienstra

doi:10.1038/ncomms5711

IL-37 protects against obesity-induced inflammation and insulin resistance

Dov B. Ballak, Janna A. Van Diepen, Alexander R. Moschen, Henry J. Jansen, Anneke Hijmans, Gert-jan Groenhof, Floris Leenders, Philip Bufler, Mark V. Boekschoten, Michael Müller, Sander Kersten, Suzhao Li, Soohyun Kim, Hadar Eini, Eli C. Lewis, Leo A. B. Joosten, Herbert Tilg, Mihai G. Netea, Cees J. Tack, Charles A. DinarelloRinke Stienstra

Research output: Contribution to journal › Article › peer-review

188 Citations (Scopus)

Abstract

Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

Original language	English
Article number	4711
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5711
Publication status	Published - 3 Sep 2014

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Cite this

Ballak, D. B., Van Diepen, J. A., Moschen, A. R., Jansen, H. J., Hijmans, A., Groenhof, G., Leenders, F., Bufler, P., Boekschoten, M. V., Müller, M., Kersten, S., Li, S., Kim, S., Eini, H., Lewis, E. C., Joosten, L. A. B., Tilg, H., Netea, M. G., Tack, C. J., ... Stienstra, R. (2014). IL-37 protects against obesity-induced inflammation and insulin resistance. Nature Communications, 5, [4711]. https://doi.org/10.1038/ncomms5711

Ballak, Dov B. ; Van Diepen, Janna A. ; Moschen, Alexander R. ; Jansen, Henry J. ; Hijmans, Anneke ; Groenhof, Gert-jan ; Leenders, Floris ; Bufler, Philip ; Boekschoten, Mark V. ; Müller, Michael ; Kersten, Sander ; Li, Suzhao ; Kim, Soohyun ; Eini, Hadar ; Lewis, Eli C. ; Joosten, Leo A. B. ; Tilg, Herbert ; Netea, Mihai G. ; Tack, Cees J. ; Dinarello, Charles A. ; Stienstra, Rinke. / IL-37 protects against obesity-induced inflammation and insulin resistance. In: Nature Communications. 2014 ; Vol. 5.

@article{a6341cf7b2fe4db0abe09a0ad749b49d,

title = "IL-37 protects against obesity-induced inflammation and insulin resistance",

abstract = "Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.",

author = "Ballak, {Dov B.} and {Van Diepen}, {Janna A.} and Moschen, {Alexander R.} and Jansen, {Henry J.} and Anneke Hijmans and Gert-jan Groenhof and Floris Leenders and Philip Bufler and Boekschoten, {Mark V.} and Michael M{\"u}ller and Sander Kersten and Suzhao Li and Soohyun Kim and Hadar Eini and Lewis, {Eli C.} and Joosten, {Leo A. B.} and Herbert Tilg and Netea, {Mihai G.} and Tack, {Cees J.} and Dinarello, {Charles A.} and Rinke Stienstra",

year = "2014",

month = sep,

day = "3",

doi = "10.1038/ncomms5711",

language = "English",

volume = "5",

journal = "Nature Communications",

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Ballak, DB, Van Diepen, JA, Moschen, AR, Jansen, HJ, Hijmans, A, Groenhof, G, Leenders, F, Bufler, P, Boekschoten, MV, Müller, M, Kersten, S, Li, S, Kim, S, Eini, H, Lewis, EC, Joosten, LAB, Tilg, H, Netea, MG, Tack, CJ, Dinarello, CA & Stienstra, R 2014, 'IL-37 protects against obesity-induced inflammation and insulin resistance', Nature Communications, vol. 5, 4711. https://doi.org/10.1038/ncomms5711

IL-37 protects against obesity-induced inflammation and insulin resistance. / Ballak, Dov B.; Van Diepen, Janna A.; Moschen, Alexander R.; Jansen, Henry J.; Hijmans, Anneke; Groenhof, Gert-jan; Leenders, Floris; Bufler, Philip; Boekschoten, Mark V.; Müller, Michael; Kersten, Sander; Li, Suzhao; Kim, Soohyun; Eini, Hadar; Lewis, Eli C.; Joosten, Leo A. B.; Tilg, Herbert; Netea, Mihai G.; Tack, Cees J.; Dinarello, Charles A.; Stienstra, Rinke.

In: Nature Communications, Vol. 5, 4711, 03.09.2014.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - IL-37 protects against obesity-induced inflammation and insulin resistance

AU - Ballak, Dov B.

AU - Van Diepen, Janna A.

AU - Moschen, Alexander R.

AU - Jansen, Henry J.

AU - Hijmans, Anneke

AU - Groenhof, Gert-jan

AU - Leenders, Floris

AU - Bufler, Philip

AU - Boekschoten, Mark V.

AU - Müller, Michael

AU - Kersten, Sander

AU - Li, Suzhao

AU - Kim, Soohyun

AU - Eini, Hadar

AU - Lewis, Eli C.

AU - Joosten, Leo A. B.

AU - Tilg, Herbert

AU - Netea, Mihai G.

AU - Tack, Cees J.

AU - Dinarello, Charles A.

AU - Stienstra, Rinke

PY - 2014/9/3

Y1 - 2014/9/3

N2 - Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

AB - Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

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DO - 10.1038/ncomms5711

M3 - Article

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JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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ER -