Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice.
BACKGROUND
Chronic low-grade inflammation involving adipose tissue likely contributes to the metabolic consequences of obesity. The cytokine interleukin (IL)-33 and its receptor ST2 are expressed in adipose tissue, but their role in adipose tissue inflammation during obesity is unclear.


OBJECTIVE
To examine the functional role of IL-33 in adipose tissues and investigate the effects on adipose tissue inflammation and obesity in vivo.


RESULTS
We demonstrate that treatment of adipose tissue cultures in vitro with IL-33 induced production of Th2 cytokines (IL-5, IL-13, IL-10) and reduced expression of adipogenic and metabolic genes. Administration of recombinant IL-33 to genetically obese diabetic (ob/ob) mice led to reduced adiposity, reduced fasting glucose and improved glucose and insulin tolerance. IL-33 also induced accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages toward an M2 alternatively activated phenotype (CD206(+)), a lineage associated with protection against obesity-related metabolic events. Furthermore, mice lacking endogenous ST2 fed high-fat diet had increased body weight and fat mass and impaired insulin secretion and glucose regulation compared to WT controls fed high-fat diet.


CONCLUSIONS
In conclusion, IL-33 may play a protective role in the development of adipose tissue inflammation during obesity.
Miller
Ashley M
AM
Division of Immunology, Infection and Inflammation, GBRC, University of Glasgow, Glasgow, United Kingdom. a.miller@clinmed.gla.ac.uk
Asquith
Darren L
DL
Hueber
Axel J
AJ
Anderson
Lesley A
LA
Holmes
William M
WM
McKenzie
Andrew N
AN
Xu
Damo
D
Sattar
Naveed
N
McInnes
Iain B
IB
Liew
Foo Y
FY
D050156:Adipogenesis / Q000235:genetics; D052436:Adipose Tissue, White / Q000276:immunology* / Q000503:physiopathology; D050154:Adiposity / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007333:Insulin Resistance / Q000235:genetics; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000008:administration & dosage / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D015434:Panniculitis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
D001786:Blood Glucose; D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D011994:Recombinant Proteins