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

被引：198

作者：

Ballak, Dov B. ^{[1
]}

van Diepen, Janna A. ^{[1
]}

Moschen, Alexander R. ^{[2
]}

Jansen, Henry J. ^{[1
]}

Hijmans, Anneke ^{[1
]}

Groenhof, Gert-Jan ^{[1
]}

Leenders, Floris ^{[1
]}

Bufler, Philip ^{[2
]}

Boekschoten, Mark V. ^{[3
]}

Muller, Michael ^{[3
]}

Kersten, Sander ^{[3
]}

Li, Suzhao ^{[4
]}

Kim, SooHyun ^{[5
]}

Eini, Hadar ^{[6
]}

Lewis, Eli C. ^{[6
]}

Joosten, Leo A. B. ^{[1
]}

Tilg, Herbert ^{[7
]}

Netea, Mihai G. ^{[1
]}

Tack, Cees J. ^{[1
]}

Dinarello, Charles A. ^{[1
,4
]}

Stienstra, Rinke ^{[1
,3
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6500 HB Nijmegen, Netherlands

[2] Univ Munich, Childrens Hosp, D-80337 Munich, Germany

[3] Wageningen Univ, Dept Human Nutr, NL-6703 HD Wageningen, Netherlands

[4] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA

[5] Konkuk Univ, Dept Biomed Sci & Technol, Seoul 143701, South Korea

[6] Ben Gurion Univ Negev, Dept Clin Biochem, IL-84105 Beer Sheva, Israel

[7] Med Univ Innsbruck, Christian Doppler Res Lab Gut Inflammat, A-6020 Innsbruck, Austria

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

WHITE ADIPOSE-TISSUE; INNATE IMMUNITY; FAMILY-MEMBER; RECEPTOR; MICE; FAT; EXPRESSION; BETA; AMPK; IDENTIFICATION;

D O I：

10.1038/ncomms5711

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 62 条

[1] Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity [J].

Arita, Y ;

Kihara, S ;

Ouchi, N ;

Takahashi, M ;

Maeda, K ;

Miyagawa, J ;

Hotta, K ;

Shimomura, I ;

Nakamura, T ;

Miyaoka, K ;

Kuriyama, H ;

Nishida, M ;

Yamashita, S ;

Okubo, K ;

Matsubara, K ;

Muraguchi, M ;

Ohmoto, Y ;

Funahashi, T ;

Matsuzawa, Y .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 257 (01) :79-83

[2] Brown adipose tissue activity controls triglyceride clearance [J].

Bartelt, Alexander ;

Bruns, Oliver T. ;

Reimer, Rudolph ;

Hohenberg, Heinz ;

Ittrich, Harald ;

Peldschus, Kersten ;

Kaul, Michael G. ;

Tromsdorf, Ulrich I. ;

Weller, Horst ;

Waurisch, Christian ;

Eychmueller, Alexander ;

Gordts, Philip L. S. M. ;

Rinninger, Franz ;

Bruegelmann, Karoline ;

Freund, Barbara ;

Nielsen, Peter ;

Merkel, Martin ;

Heeren, Joerg .

NATURE MEDICINE, 2011, 17 (02) :200-U93

[3] Interleukin-1 homologues lL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharide [J].

Bufler, P ;

Gamboni-Robertson, F ;

Azam, T ;

Kim, SH ;

Dinarello, CA .

BIOCHEMICAL JOURNAL, 2004, 381 :503-510

[4] Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses [J].

Bulau, Ana-Maria ;

Nold, Marcel F. ;

Li, Suzhao ;

Nold-Petry, Claudia A. ;

Fink, Michaela ;

Mansell, Ashley ;

Schwerd, Tobias ;

Hong, Jaewoo ;

Rubartelli, Anna ;

Dinarello, Charles A. ;

Bufler, Philip .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (07) :2650-2655

[5] Identification and gene organization of three novel members of the IL-1 family on human chromosome 2 [J].

Busfield, SJ ;

Comrack, CA ;

Yu, G ;

Chickering, TW ;

Smutko, JS ;

Zhou, H ;

Leiby, KR ;

Holmgren, LM ;

Gearing, DP ;

Pan, Y .

GENOMICS, 2000, 66 (02) :213-216

[6] Inhibition of toll-like receptor 2 expression improves insulin sensitivity and signaling in muscle and white adipose tissue of mice fed a high-fat diet [J].

Caricilli, Andrea M. ;

Nascimento, Paula H. ;

Pauli, Jose R. ;

Tsukumo, Daniela M. L. ;

Velloso, Licio A. ;

Carvalheira, Jose B. ;

Saad, Mario J. A. .

JOURNAL OF ENDOCRINOLOGY, 2008, 199 (03) :399-406

[7] The role of AMP-activated protein kinase in regulating white adipose tissue metabolism [J].

Ceddia, R. B. .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2013, 366 (02) :194-203

[8] Interleukin-37 [J].

Dinarello, Charles A. ;

Bufler, Philip .

SEMINARS IN IMMUNOLOGY, 2013, 25 (06) :466-468

[9] Interleukin-1 in the pathogenesis and treatment of inflammatory diseases [J].

Dinarello, Charles A. .

BLOOD, 2011, 117 (14) :3720-3732

[10] Type 2 diabetes as an inflammatory disease [J].

Donath, Marc Y. ;

Shoelson, Steven E. .

NATURE REVIEWS IMMUNOLOGY, 2011, 11 (02) :98-107

← 1 2 3 4 5 6 7 →