Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice.
BACKGROUND
Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Natural killer T (NKT) cells, which integrate proinflammatory cytokines, have been demonstrated in the atherosclerotic lesions and in visceral adipose tissue.


OBJECTIVE
To determine whether NKT cells are involved in glucose intolerance and adipose tissue inflammation in diet-induced obese mice.


RESULTS
Male beta(2)-microglobulin knockout (KO) mice lacking NKT cells and C57BL/6J (wild-type) mice were fed with a high-fat diet (HFD) for 13 weeks [corrected]. Body weight and visceral obesity were comparable between wild-type and KO mice. However, macrophage infiltration was reduced in adipose tissue and glucose intolerance was significantly ameliorated in KO mice. To further confirm that NKT cells are involved in these abnormalities, alpha-galactosylceramide, 0.1 microg/g body weight, which specifically activates NKT cells, was administered after 13 weeks of HFD feeding. alpha-Galactosylceramide significantly exacerbated glucose intolerance and macrophage infiltration as well as cytokine gene expression in adipose tissue.


CONCLUSIONS
NKT cells play a crucial role in the development of adipose tissue inflammation and glucose intolerance in diet-induced obesity.
Ohmura
Kazue
K
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Ishimori
Naoki
N
Ohmura
Yoshinori
Y
Tokuhara
Satoshi
S
Nozawa
Atsushi
A
Horii
Shunpei
S
Andoh
Yasuhiro
Y
Fujii
Satoshi
S
Iwabuchi
Kazuya
K
Onoé
Kazunori
K
Tsutsui
Hiroyuki
H
D000818:Animals; D016207:Cytokines / Q000235:genetics; D004041:Dietary Fats; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000494:pharmacology; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000276:immunology* / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D009765:Obesity / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D016207:Cytokines; D004041:Dietary Fats; D005699:Galactosylceramides; D012333:RNA, Messenger; D001613:beta 2-Microglobulin