@article{41b1d63b6710457fbadb6227d662efa3,
title = "Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance",
abstract = "Recent studies of obesity have provided new insights into the mechanisms underlying insulin resistance and metabolic dysregulation. Numerous efforts have been made to identify key regulators of obesity-linked adipose tissue inflammation and insulin resistance. We found that angiopoietin-like protein 2 (Angptl2) was secreted by adipose tissue and that its circulating level was closely related to adiposity, systemic insulin resistance, and inflammation in both mice and humans. Angptl2 activated an inflammatory cascade in endothelial cells via integrin signaling and induced chemotaxis of monocytes/macrophages. Constitutive Angptl2 activation in vivo induced inflammation of the vasculature characterized by abundant attachment of leukocytes to the vessel walls and increased permeability. Angptl2 deletion ameliorated adipose tissue inflammation and systemic insulin resistance in diet-induced obese mice. Conversely, Angptl2 overexpression in adipose tissue caused local inflammation and systemic insulin resistance in nonobese mice. Thus, Angptl2 is a key adipocyte-derived inflammatory mediator that links obesity to systemic insulin resistance.",
keywords = "HUMDISEASE",
author = "Mitsuhisa Tabata and Tsuyoshi Kadomatsu and Shigetomo Fukuhara and Keishi Miyata and Yasuhiro Ito and Motoyoshi Endo and Takashi Urano and Zhu, {Hui Juan} and Hiroto Tsukano and Hirokazu Tazume and Koichi Kaikita and Kazuya Miyashita and Takao Iwawaki and Michio Shimabukuro and Kazuhiko Sakaguchi and Takaaki Ito and Naomi Nakagata and Tetsuya Yamada and Hideki Katagiri and Masato Kasuga and Yukio Ando and Hisao Ogawa and Naoki Mochizuki and Hiroshi Itoh and Toshio Suda and Yuichi Oike",
note = "Funding Information: We would like to thank Ms. K. Fukushima, I. Ishimatsu, R. Shindo, Y. Indo, S. Iwaki, and O. Takahashi for experimental assistance; and Drs. S. Fuchigami, K. Yasunaga, N. Yamaji, and A. Sakurai for experimental assistance and helpful discussion. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas (17014078) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by Grants-in Aid for Scientific Research (B) (21390245) from Japan Society for Promotion of Science; by a grant from the Mochida Memorial Foundation; by a grant from the Takeda Science Foundation; by a grant from the Sumitomo Foundation; by a grant from the Uehara Memorial Foundation; and by a grant from the Cell Science Research Foundation. ",
year = "2009",
month = sep,
day = "2",
doi = "10.1016/j.cmet.2009.08.003",
language = "English",
volume = "10",
pages = "178--188",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}
