ID 110149
著者
ニシモト, サチコ Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School
福田, 大受 Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
ヒガシクニ, ヤストミ Department of Cardiovascular Medicine, The University of Tokyo
タナカ, キミエ Division for Health Service Promotion, The University of Tokyo
ヒラタ, ヨウイチロウ Department of Pediatrics, The University of Tokyo Hospital
ムラタ, チエ Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School
Kim-Kaneyama, Joo-ri Department of Biochemistry, Showa University School of Medicine
サトウ, フキコ Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School
バンドウ, マサヒロ Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School
八木, 秀介 Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
添木, 武 Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
ハヤシ, テツヤ Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences
井本, 逸勢 Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
阪上, 浩 Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
シマブクロ, ミチオ Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School|Diabetes and Lifestyle-Related Disease Center, Tomishiro Central Hospital
佐田, 政隆 Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
cell-free DNA
inflammation
adipose tissue
insulin resistance
macrophage
Toll-like receptor-9
資料タイプ
学術雑誌論文
抄録
Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9−/−) macrophages. Fat-fed Tlr9−/− mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9−/− mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography–determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.
掲載誌名
Science Advances
ISSN
23752548
2
3
開始ページ
e1501332
並び順
1501332
発行日
2016-03-25
備考
Copyright: 2016 © The Authors, some rights reserved;exclusive licensee American Association forthe Advancement of Science. Distributedunder a Creative Commons AttributionNonCommercial License 4.0 (CC BY-NC).
EDB ID
310765
出典
Science Advances (2016) Vol.2 No.3 e1501332
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系