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 Kasuga; Yukio Ando; Hisao Ogawa; Naoki Mochizuki; Hiroshi Itoh; Toshio Suda; Yuichi Oike

doi:10.1016/j.cmet.2009.08.003

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 journal › Article › peer-review

289 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 language	English
Pages (from-to)	178-188
Number of pages	11
Journal	Cell Metabolism
Volume	10
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2009.08.003
Publication status	Published - 2009 Sept 2
Externally published	Yes

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmet.2009.08.003

Cite this

Tabata, M., Kadomatsu, T., Fukuhara, S., Miyata, K., Ito, Y., Endo, M., Urano, T., Zhu, H. J., Tsukano, H., Tazume, H., Kaikita, K., Miyashita, K., Iwawaki, T., Shimabukuro, M., Sakaguchi, K., Ito, T., Nakagata, N., Yamada, T., Katagiri, H., ... Oike, Y. (2009). Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance. Cell Metabolism, 10(3), 178-188. https://doi.org/10.1016/j.cmet.2009.08.003

Tabata, M, Kadomatsu, T, Fukuhara, S, Miyata, K, Ito, Y, Endo, M, Urano, T, Zhu, HJ, Tsukano, H, Tazume, H, Kaikita, K, Miyashita, K, Iwawaki, T, Shimabukuro, M, Sakaguchi, K, Ito, T, Nakagata, N, Yamada, T, Katagiri, H, Kasuga, M, Ando, Y, Ogawa, H, Mochizuki, N, Itoh, H, Suda, T & Oike, Y 2009, 'Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance', Cell Metabolism, vol. 10, no. 3, pp. 178-188. https://doi.org/10.1016/j.cmet.2009.08.003

@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",

}

TY - JOUR

T1 - Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance

AU - Tabata, Mitsuhisa

AU - Kadomatsu, Tsuyoshi

AU - Fukuhara, Shigetomo

AU - Miyata, Keishi

AU - Ito, Yasuhiro

AU - Endo, Motoyoshi

AU - Urano, Takashi

AU - Zhu, Hui Juan

AU - Tsukano, Hiroto

AU - Tazume, Hirokazu

AU - Kaikita, Koichi

AU - Miyashita, Kazuya

AU - Iwawaki, Takao

AU - Shimabukuro, Michio

AU - Sakaguchi, Kazuhiko

AU - Ito, Takaaki

AU - Nakagata, Naomi

AU - Yamada, Tetsuya

AU - Katagiri, Hideki

AU - Kasuga, Masato

AU - Ando, Yukio

AU - Ogawa, Hisao

AU - Mochizuki, Naoki

AU - Itoh, Hiroshi

AU - Suda, Toshio

AU - Oike, Yuichi

N1 - 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.

PY - 2009/9/2

Y1 - 2009/9/2

N2 - 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.

AB - 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.

KW - HUMDISEASE

UR - http://www.scopus.com/inward/record.url?scp=69149090011&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69149090011&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2009.08.003

DO - 10.1016/j.cmet.2009.08.003

M3 - Article

C2 - 19723494

AN - SCOPUS:69149090011

SN - 1550-4131

VL - 10

SP - 178

EP - 188

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this