FGF-1 in human adipogenesis

肥胖在澳大利亚成年人和儿童中变得越来越普遍，是包括2型糖尿病、心血管疾病和一些癌症在内的许多疾病的主要诱因。目前使用生活方式改变(饮食和锻炼)或药物的减肥策略对大多数肥胖者来说相对无效。这在一定程度上是因为我们对控制人体体重的因素知之甚少。在实验室研究中，我们已经证明成纤维细胞生长因子-1可以显著加速人类脂肪细胞的发育。这种生长因子是由人体内皮细胞产生的，内皮细胞是脂肪组织中排列血管的细胞。当人类脂肪细胞前体细胞(前体脂肪细胞)在含有成纤维细胞生长因子-1的情况下培养时，前体脂肪细胞的分裂速度比正常快得多，然后发育成成熟脂肪细胞的速度也比正常快得多。这些过程涉及到新脂肪细胞的发展，形成了体内脂肪组织扩张的基础。成纤维细胞生长因子-1对人类脂肪细胞发育的影响远远大于其他已知的促进脂肪细胞生长的因素。该项目的目的是确定介导成纤维细胞生长因子-1促进脂肪细胞生长和发育的实际生化途径。所获得的结果将为深入了解调节人类脂肪组织质量膨胀的细胞和分子机制提供依据。旨在确定这些潜在机制，或潜在的促进或加剧因素的研究，对于开发新的、更有效的预防和治疗肥胖症的方法至关重要。

Obesity is becoming more common in Australian adults and children, and is a major contributor to a number of diseases including type 2 diabetes, cardiovascular disease and some cancers. Current weight loss strategies using either lifestyle modification (diet and exercise) or drugs are relatively ineffective in the majority of obese individuals. This is partly due to the fact that we have an incomplete knowledge of the factors that regulate weight in humans. In laboratory studies we have shown that human fat cell development can be dramatically accelerated by fibroblast growth factor-1 (FGF-1). This growth factor is produced by human endothelial cells, which are cells that line the blood vessels in fat tissue. When human fat cell precursors (preadipocytes) are cultured in the presence of FGF-1 the preadipocytes divide much more rapidly than normal and, additionally, then develop into mature fat cells much more rapidly than normal. These processes involved in development of new fat cells form the basis of fat tissue expansion in the body. The effect of FGF-1 on human fat cell development is far greater in magnitude than that of other known factors that promote fat cell growth. The aim of this project is to determine the actual biochemical pathways that mediate the effect of FGF-1 in promoting fat cell growth and development. Results obtained will provide insight into the cellular and molecular mechanisms regulating expansion of fat tissue mass in humans. Research aimed at identifying these underlying mechanisms, or at potentially contributing or exacerbating factors, is critically important in development of novel and more effective approaches to prevention and treatment of obesity.