Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity.
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-A(b), a mouse class II histocompatibility marker implicated in antigen presentation, as determined by immunostaining. Differentiated 3T3-L1 cells stimulated with recombinant IFNgamma or T-helper 1-derived supernatant produced several chemokines and their mRNAs. Obese IFNgamma-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 IFNgamma 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 IFNgamma-inducible protein-10 and I-A(b), and lower plasma triglycerides and glucose. These results indicate a role for T cells and IFNgamma, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity.
Rocha
Viviane Zorzanelli
VZ
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, 02115, USA.
Folco
Eduardo J
EJ
Sukhova
Galina
G
Shimizu
Koichi
K
Gotsman
Israel
I
Vernon
Ashley H
AH
Libby
Peter
P
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015870:Gene Expression / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020738:Leptin / Q000097:blood; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000276:immunology* / Q000378:metabolism; D009924:Organ Culture Techniques; D017471:Receptors, Interferon / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000096743:Interferon gamma Receptor
D001057:Apolipoproteins E; D001786:Blood Glucose; D002784:Cholesterol; D007371:Interferon-gamma; D020738:Leptin; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor