Novel regulators of fat cell differentiation

脂肪细胞分化的新型调节剂

• 批准号: nhmrc : 457373
• 负责人: A/Pr Susan Mclennan
• 金额: $ 29.71万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-regulators-fat-cell-differentiation/81456
• 关键词: Novel; regulators; fat; cell; differentiation

Overweight and obesity are at epidemic proportions in Australia, reflecting the pattern in the developed and developing world. The main cause appears to be an energy mismatch, with excessive caloric consumption. One response of the body to excessive nutrient supply is energy storage in fat tissue and to aid in this the body also generates new fat tissue, termed adipogenesis (also known in cells as fat cell differentiation). In many people who gain excess body weight, fat tissue is abnormal and does not respond well to the chemical insulin, thus causing insulin resistance. This insulin resistant fat tissue is especially present in a central body (visceral) site. Insulin resistance related to this visceral fat predisposes to both diabetes and premature death from cardiovascular disease. Understanding how fat tissue develops and how it might cause insulin resistance is thus important in human health. One of the factors in fat that prevents normal development of fat tissue and which induces insulin resistance is transforming growth factor- (TGF- ). We have generated new data showing that two proteins which are increased by TGF- , termed connective tissue growth factor (CTGF) and insulin like growth factor binding protein-3, (IGFBP-3), prevent adipogenesis. We have shown this in cultured cells, and have found that CTGF and IGFBP-3 are increased in visceral fat in animal models of obesity and insulin resistance. Our preliminary work has further indicated how CTGF and IGFBP-3 might each work in the fat cell to prevent adipogenesis. This proposal will determine if TGF- works through CTGF and IGFBP-3 to block adipogenesis, and it will define how CTGF and IGFBP-3 have their inhibitory effects on fat cell differentiation. Cells in culture will be utilised and an animal model of dietary induced obesity and insulin resistance will help to define whether CTGF and IGFBP-3 prevent adipogenesis in vivo, furthering our understanding in how abnormal fat tissue may develop.

超重和肥胖在澳大利亚很普遍，反映了发达国家和发展中国家的模式。主要原因似乎是能量不匹配，热量消耗过多。身体对过度营养供应的一种反应是在脂肪组织中储存能量，并且为了帮助身体产生新的脂肪组织，称为脂肪生成（在细胞中也称为脂肪细胞分化）。在许多体重增加过多的人中，脂肪组织出现异常，对化学胰岛素反应不佳，从而导致胰岛素抵抗。这种胰岛素抵抗脂肪组织尤其存在于身体中央（内脏）部位。与这种内脏脂肪相关的胰岛素抵抗容易导致糖尿病和因心血管疾病而过早死亡。因此，了解脂肪组织如何发育以及它如何导致胰岛素抵抗对于人类健康非常重要。脂肪中阻止脂肪组织正常发育并诱导胰岛素抵抗的因素之一是转化生长因子（TGF-）。我们生成的新数据显示，TGF-β 增加的两种蛋白质，即结缔组织生长因子 (CTGF) 和胰岛素样生长因子结合蛋白 3 (IGFBP-3)，可防止脂肪形成。我们在培养细胞中证明了这一点，并发现肥胖和胰岛素抵抗动物模型的内脏脂肪中 CTGF 和 IGFBP-3 增加。我们的初步工作进一步表明 CTGF 和 IGFBP-3 如何在脂肪细胞中各自发挥作用以防止脂肪生成。该提案将确定 TGF-β 是否通过 CTGF 和 IGFBP-3 阻止脂肪生成，并将定义 CTGF 和 IGFBP-3 如何对脂肪细胞分化产生抑制作用。将利用培养细胞，饮食诱导的肥胖和胰岛素抵抗的动物模型将有助于确定 CTGF 和 IGFBP-3 是否能阻止体内脂肪生成，从而进一步加深我们对异常脂肪组织如何形成的理解。