Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance

Mitsuhisa Tabata, Tsuyoshi Kadomatsu, Shigetomo Fukuhara, Keishi Miyata, Yasuhiro Ito, Motoyoshi Endo, Takashi Urano, Hui Juan Zhu, Hiroto Tsukano, Hirokazu Tazume, Koichi Kaikita, Kazuya Miyashita, Takao Iwawaki, Michio Shimabukuro, Kazuhiko Sakaguchi, Takaaki Ito, Naomi Nakagata, Tetsuya Yamada, Hideki Katagiri, Masato KasugaYukio Ando, Hisao Ogawa, Naoki Mochizuki, Hiroshi Itoh, Toshio Suda, Yuichi Oike

Research output: Contribution to journalArticlepeer-review

234 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)178-188
Number of pages11
JournalCell Metabolism
Volume10
Issue number3
DOIs
Publication statusPublished - 2009 Sep 2

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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