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PMID: 17823662 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 117 ·No. 10 ·2007-10-00 ·Pages 2877-88

Nomiyama T, Perez-Tilve D, Ogawa D, Gizard F, Zhao Y, Heywood EB, Jones KL, Kawamori R, Cassis LA, Tschöp MH, Bruemmer D

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.

MeSH Terms
Adipose Tissue/immunology Animals Chemokine CCL2/metabolism Chemotaxis/genetics Dietary Fats/administration & dosage Inflammation/genetics,immunology Insulin Resistance/immunology Macrophages/immunology Mice Mice, Mutant Strains Obesity/complications,immunology Osteopontin/genetics,physiology
Chemicals
Ccl2 protein, mouse Chemokine CCL2 Dietary Fats Osteopontin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Nomiyama Takashi
Division of Endocrinology and Molecular Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
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
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI31986
Published
2007-10-00
Pages
2877-88
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1964510
Subset
IM
Grants
NHLBI NIH HHS · R01 HL084611 · United States
NIDDK NIH HHS · U24 DK059630 · United States
NIDDK NIH HHS · DK59630 · United States
NHLBI NIH HHS · HL084611 · United States
External Links
PubMed source DOI: 10.1172/JCI31986 PMC Full Text View journal details
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