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; Soo Hyun 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, Soo Hyun Kim, Hadar Eini, Eli C. Lewis, Leo A.B. Joosten, Herbert Tilg, Mihai G. Netea, Cees J. Tack, Charles A. DinarelloRinke Stienstra

Department of Clinical Biochemistry and Pharmacology

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

166 Scopus citations

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
State	Published - 3 Sep 2014

ASJC Scopus subject areas

Chemistry (all)
Biochemistry, Genetics and Molecular Biology (all)
General
Physics and Astronomy (all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms5711

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Ballak, D. B., Van Diepen, J. A., Moschen, A. R., Jansen, H. J., Hijmans, A., Groenhof, G. J., Leenders, F., Bufler, P., Boekschoten, M. V., Müller, M., Kersten, S., Li, S., Kim, S. H., 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

@article{d1a9b55d22184abd8d2941173d3b891a,

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 Groenhof, {Gert Jan} and Floris Leenders and Philip Bufler and Boekschoten, {Mark V.} and Michael M{\"u}ller and Sander Kersten and Suzhao Li and Kim, {Soo Hyun} 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",

note = "Funding Information: R.S. was supported by a Ruby Grant of the Dutch Diabetes Research Foundation. M.G.N. was supported by a Vici Grant from the Netherlands Organization for Scientific Research (NWO). P.B. was supported by Deutsche Forschungsgemeinschaft BU 1222/3-3. We thank Tim Koenen for help in collecting the human adipose samples.",

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, GJ, Leenders, F, Bufler, P, Boekschoten, MV, Müller, M, Kersten, S, Li, S, Kim, SH, 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

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, Soo Hyun

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

N1 - Funding Information: R.S. was supported by a Ruby Grant of the Dutch Diabetes Research Foundation. M.G.N. was supported by a Vici Grant from the Netherlands Organization for Scientific Research (NWO). P.B. was supported by Deutsche Forschungsgemeinschaft BU 1222/3-3. We thank Tim Koenen for help in collecting the human adipose samples.

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.

UR - http://www.scopus.com/inward/record.url?scp=84907356510&partnerID=8YFLogxK

U2 - 10.1038/ncomms5711

DO - 10.1038/ncomms5711

M3 - Article

AN - SCOPUS:84907356510

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4711

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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