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.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Tabata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kadomatsu
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Endo
authors.forename: Takashi
authors.initials: T
authors.lastname: Urano
authors.forename: Hui Juan
authors.initials: HJ
authors.lastname: Zhu
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tsukano
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tazume
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miyashita
authors.forename: Takao
authors.initials: T
authors.lastname: Iwawaki
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
mesh_terms: D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D016023:Integrins / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D016023:Integrins