The roles of integrin receptors in adipocyte differentiation

需要检验的假设是，两种蛋白质，整合素a5和整合素a6共同作用，控制 脂肪细胞的形成。肥胖是美国的一个主要医疗保健问题，与肥胖密切相关 有许多健康问题，如癌症、心血管疾病、高血压，特别是糖尿病。 当能量输入超过能量消耗，导致更多的脂肪细胞和更大的脂肪细胞时，肥胖就会发生。 脂肪产生的第一步涉及间充质干细胞的增殖，随后分化为 脂肪细胞前体称为前体脂肪细胞。然后，前脂肪细胞在脂肪产生的地方迁移和增殖， 在那里它们进一步分化为球形脂肪细胞。这一多步骤的过程受 许多激素，并伴随着细胞形状和基因表达的戏剧性变化。我们有 最近发现了一个从整合素α5到整合素α6的基因活性的关键开关。该开关允许 前脂肪细胞停止分裂和聚集，形成真正的脂肪细胞。整合素是细胞表面蛋白， 参与与细胞外蛋白质网络的结合，这可能会影响它们的行为。许多 在脂肪细胞的产生过程中会发生一些事情，我们相信从一种整合素到另一种整合素的转变是一种 关键的一步。在这里，我们提出了操纵这两个整合素的实验，并检查了它们对 脂肪细胞的形成。更全面地了解脂肪形成过程中发生的事情为 肥胖症和糖尿病的治疗。

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.