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- Title
Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice.
- Authors
Nomiyama, Takashi; Perez-Tilve, Diego; Ogawa, Daisuke; Gizard, Florence; Yue Zhao; Heywood, Elizabeth B.; Jones, Karrie L.; Kawamori, Ryuzo; Cassis, Lisa A.; Tschöp, Matthias H.; Bruemmer, Dennis; Zhao, Yue; Tschöp, Matthias H
- 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.
- Subjects
OSTEOPONTIN; OBESITY; ADIPOSE tissues; MACROPHAGES; INSULIN resistance; LABORATORY mice; CYTOKINES; DISEASE risk factors; OBESITY complications; ANIMAL experimentation; CELL physiology; COMPARATIVE studies; FAT content of food; INFLAMMATION; INFLAMMATORY mediators; RESEARCH methodology; MEDICAL cooperation; MICE; PROTEINS; RESEARCH; EVALUATION research
- Publication
Journal of Clinical Investigation, 2007, Vol 117, Issue 10, p2877
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI31986