| First Author | Féral CC | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 7 | Pages | 1842-51 |
| PubMed ID | 18426864 | Mgi Jnum | J:138251 |
| Mgi Id | MGI:3804608 | Doi | 10.2337/db07-1751 |
| Citation | Feral CC, et al. (2008) Blockade of alpha4 integrin signaling ameliorates the metabolic consequences of high-fat diet-induced obesity. Diabetes 57(7):1842-51 |
| abstractText | OBJECTIVE: Many prevalent diseases of advanced societies, such as obesity-induced type 2 diabetes, are linked to indolent mononuclear cell-dependent inflammation. We previously proposed that blockade of alpha4 integrin signaling can inhibit inflammation while limiting mechanism-based toxicities of loss of alpha4 function. Thus, we hypothesized that mice bearing an alpha4(Y991A) mutation, which blocks signaling, would be protected from development of high-fat diet-induced insulin resistance. RESEARCH DESIGN AND METHODS: Six- to eight-week-old wild-type and alpha4(Y991A) C57Bl/6 male mice were placed on either a high-fat diet that derived 60% calories from lipids or a chow diet. Metabolic testing was performed after 16-22 weeks of diet. RESULTS: Alpha4(Y991A) mice were protected from development of high-fat diet-induced insulin resistance. This protection was conferred on wild-type mice by alpha4(Y991A) bone marrow transplantation. In the reverse experiment, wild-type bone marrow renders high-fat diet-fed alpha4(Y991A) acceptor animals insulin resistant. Furthermore, fat-fed alpha4(Y991A) mice showed a dramatic reduction of monocyte/macrophages in adipose tissue. This reduction was due to reduced monocyte/macrophage migration rather than reduced monocyte chemoattractant protein-1 production. CONCLUSIONS: Alpha4 integrins contribute to the development of HFD-induced insulin resistance by mediating the trafficking of monocytes into adipose tissue; hence, blockade of alpha4 integrin signaling can prevent the development of obesity-induced insulin resistance. |
