The hypothesis to be tested is that two proteins, integrin a5 and integrin a6, work together to control the formation of fat cells. Obesity is a major health care problem in the United States and is closed associated with many health problems such as cancer, cardiovascular disease, hypertension, and especially diabetes. Obesity occurs when energy input exceeds energy expenditure, resulting in more fat cells and larger fat cells. The first step in fat production involves proliferation of mesenchymal stem cells, followed by differentiation into fat cell precursors called preadipocytes. Preadipocytes then migrate and proliferate at the site of fat production, where they differentiate further to become spherical adipocytes. This multi-step process is regulated by numerous hormones and is accompanied by dramatic changes in cell shape and gene expression. We have recently identified a critical switch in gene activity from integrin alpha5 to integrin alpha6. That switch allows preadipocytes to cease dividing and cluster, forming bona fide fat cells. Integrins are cell surface proteins that are involved in binding to a meshwork of proteins outside of cells that can influence their behavior. Many things happen in the generation of fat cells and we believe that the transition from one integrin to another is a crucial step. Here we propose experiments to manipulate those two integrins and examine the effects on the formation of fat cells. The fuller understanding of what happens in fat formation opens new avenues for treatment of obesity and diabetes.
|Effective start/end date||9/2/08 → 8/31/09|
- National Institute of Diabetes and Digestive and Kidney Diseases: $146,500.00
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