Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance
| Autor: | Kazuya Miyashita, Toshio Suda, Takao Iwawaki, Naoki Mochizuki, Tsuyoshi Kadomatsu, Takashi Urano, Hirokazu Tazume, Koichi Kaikita, Shigetomo Fukuhara, Hideki Katagiri, Mitsuhisa Tabata, Takaaki Ito, Hui Juan Zhu, Tetsuya Yamada, Keishi Miyata, Kazuhiko Sakaguchi, Naomi Nakagata, Masato Kasuga, Michio Shimabukuro, Yasuhiro Ito, Yukio Ando, Hiroto Tsukano, Motoyoshi Endo, Hisao Ogawa, Yuichi Oike, Hiroshi Itoh |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Integrins FGF21 Physiology Adipose tissue macrophages Adipose Tissue White HUMDISEASE Adipose tissue Mice Obese Inflammation Biology Cell Line Mice Insulin resistance In vivo Internal medicine 3T3-L1 Cells medicine Leukocytes Animals Humans Obesity Molecular Biology Angiopoietin-Like Protein 2 Adiposity Mice Knockout Endothelial Cells Chemotaxis Cell Biology medicine.disease Endocrinology Angiopoietin-like Proteins Cell culture medicine.symptom Insulin Resistance Angiopoietins |
| Zdroj: | Cell metabolism. 10(3) |
| ISSN: | 1932-7420 |
| Popis: | SummaryRecent 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. |
| Databáze: | OpenAIRE |
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