Journal
CIRCULATION RESEARCH
Volume 103, Issue 5, Pages 467-476Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.108.177105
Keywords
inflammation; obesity; adipose tissue; T cell; IFN gamma
Funding
- Foundation and National Heart, Lung, and Blood Institute [HL-34636]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [BEX 1594 04/4]
- American Heart Association Scientist Development Grant
- Roche Organ Transplantation Research Foundation
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Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher numbers of both CD4(+) and CD8(+) T cells than lean controls, monitored by flow cytometry. When stimulated in vitro, T cells from obese AT produced more interferon (IFN)gamma than those from controls. AT from obese animals also had more cells expressing I-Ab, a mouse class II histocompatibility marker implicated in antigen presentation, as determined by immunostaining. Differentiated 3T3-L1 cells stimulated with recombinant IFN gamma or T-helper 1-derived supernatant produced several chemokines and their mRNAs. Obese IFN gamma-deficient animals had significantly reduced AT expression of mRNA-encoding inflammatory genes such as tumor necrosis factor-alpha and monocyte chemoattractant protein-1, decreased AT inflammatory cell accumulation, and better glucose tolerance than control animals consuming the same diet. Obese mice doubly deficient for IFN gamma receptor and apolipoprotein (Apo) E on a mixed 129SvEv/C57BL/6 (129/B6) genetic background, despite exhibiting similar AT mRNA levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 as 129/B6-ApoE(-/-) controls, had decreased expression of important T cell-related genes, such as IFN gamma-inducible protein-10 and I-A(b), and lower plasma triglycerides and glucose. These results indicate a role for T cells and IFN gamma, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity. (Circ Res. 2008; 103: 467-476.)
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