Natural Killer T Cells Are Involved in Adipose Tissues Inflammation and Glucose Intolerance in Diet-Induced Obese Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 30; no. 2; pp. 193 - 199
• Main Authors: Ohmura, Kazue, Ishimori, Naoki, Ohmura, Yoshinori, Tokuhara, Satoshi, Nozawa, Atsushi, Horii, Shunpei, Andoh, Yasuhiro, Fujii, Satoshi, Iwabuchi, Kazuya, Onoé, Kazunori, Tsutsui, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.02.2010; Lippincott Williams & Wilkins
• Subjects: Animals; Atherosclerosis (general aspects, experimental research); beta 2-Microglobulin - deficiency; beta 2-Microglobulin - genetics; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cytokines - genetics; Dietary Fats; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fundamental and applied biological sciences. Psychology; Galactosylceramides - pharmacology; Gene Expression Regulation; Glucose Intolerance - immunology; Glucose Intolerance - physiopathology; Inflammation - immunology; Inflammation - physiopathology; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - physiopathology; Lymphocyte Activation - drug effects; Macrophages - immunology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Obesity - complications; Obesity - immunology; Obesity - physiopathology; RNA, Messenger - metabolism; Time Factors; Vertebrates: cardiovascular system; Endocrinopathy; Obesity; visceral adipose tissues; Adipose tissue; Rodentia; Nutrition disorder; glucose intolerance; Cardiovascular disease; Inflammation; natural killer T cells; Vascular disease; Natural killer cell; Vertebrata; macrophages; Mammalia; Mouse; Animal; Atherosclerosis; Impaired glucose tolerance; Nutritional status; Macrophage
• DOI: 10.1161/ATVBAHA.109.198614
• ISSN: 1079-5642

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. METHODS AND RESULTS—Male β2-microglobulin knockout (KO) mice lacking NKT cells and C57BL/6J (wild-type) mice were fed with a high-fat diet (HFD) for 13 weeks. 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, α-galactosylceramide, 0.1 μg/g body weight, which specifically activates NKT cells, was administered after 13 weeks of HFD feeding. α-Galactosylceramide significantly exacerbated glucose intolerance and macrophage infiltration as well as cytokine gene expression in adipose tissue. CONCLUSION—NKT cells play a crucial role in the development of adipose tissue inflammation and glucose intolerance in diet-induced obesity.