Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice

Takashi Nomiyama, Diego Perez-Tilve, Daisuke Ogawa, Florence Gizard, Yue Zhao, Elizabeth B. Heywood, Karrie L. Jones, Ryuzo Kawamori, Lisa A. Cassis, Matthias H. Tschöp, Dennis Bruemmer

Research output: Contribution to journalArticle

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Abstract

Obesity is associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and macrophage infiltration into adipose tissue, which may contribute to the development of insulin resistance. During immune responses, tissue infiltration by macrophages is dependent on the expression of osteopontin, an extracellular matrix protein and proinflammatory cytokine that promotes monocyte chemotaxis and cell motility. In the present study, we used a murine model of diet-induced obesity to examine the role of osteopontin in the accumulation of adipose tissue macrophages and the development of insulin resistance during obesity. Mice exposed to a high-fat diet exhibited increased plasma osteopontin levels, with elevated expression in macrophages recruited into adipose tissue. Obese mice lacking osteopontin displayed improved insulin sensitivity in the absence of an effect on diet-induced obesity, body composition, or energy expenditure. These mice further demonstrated decreased macrophage infiltration into adipose tissue, which may reflect both impaired macrophage motility and attenuated monocyte recruitment by stromal vascular cells. Finally, obese osteopontin-deficient mice exhibited decreased markers of inflammation, both in adipose tissue and systemically. Taken together, these results suggest that osteopontin may play a key role in linking obesity to the development of insulin resistance by promoting inflammation and the accumulation of macrophages in adipose tissue.

Original languageEnglish
Pages (from-to)2877-2888
Number of pages12
JournalJournal of Clinical Investigation
Volume117
Issue number10
DOIs
Publication statusPublished - Oct 1 2007
Externally publishedYes

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Osteopontin
Insulin Resistance
Adipose Tissue
Obesity
Macrophages
Inflammation
Monocytes
Cytokines
Diet
Obese Mice
Extracellular Matrix Proteins
High Fat Diet
Chemotaxis
Stromal Cells
Body Composition
Energy Metabolism
Cell Movement
Blood Vessels

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nomiyama, T., Perez-Tilve, D., Ogawa, D., Gizard, F., Zhao, Y., Heywood, E. B., ... Bruemmer, D. (2007). Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. Journal of Clinical Investigation, 117(10), 2877-2888. https://doi.org/10.1172/JCI31986

Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. / Nomiyama, Takashi; Perez-Tilve, Diego; Ogawa, Daisuke; Gizard, Florence; Zhao, Yue; Heywood, Elizabeth B.; Jones, Karrie L.; Kawamori, Ryuzo; Cassis, Lisa A.; Tschöp, Matthias H.; Bruemmer, Dennis.

In: Journal of Clinical Investigation, Vol. 117, No. 10, 01.10.2007, p. 2877-2888.

Research output: Contribution to journalArticle

Nomiyama, T, Perez-Tilve, D, Ogawa, D, Gizard, F, Zhao, Y, Heywood, EB, Jones, KL, Kawamori, R, Cassis, LA, Tschöp, MH & Bruemmer, D 2007, 'Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice', Journal of Clinical Investigation, vol. 117, no. 10, pp. 2877-2888. https://doi.org/10.1172/JCI31986
Nomiyama, Takashi ; Perez-Tilve, Diego ; Ogawa, Daisuke ; Gizard, Florence ; Zhao, Yue ; Heywood, Elizabeth B. ; Jones, Karrie L. ; Kawamori, Ryuzo ; Cassis, Lisa A. ; Tschöp, Matthias H. ; Bruemmer, Dennis. / Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 10. pp. 2877-2888.
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