Early Origins of Obesity

在过去的十年中，超重和肥胖人群的数量大幅增加。肥胖现在是澳大利亚的一个主要公共卫生问题，与相关的2型糖尿病和心脏病疾病一起，造成了巨大的卫生保健费用。人们普遍意识到这个问题，但事实证明很难控制这种肥胖流行病，除非我们能了解潜在的原因，否则这种趋势似乎会继续下去。这项研究计划旨在确定导致肥胖发展的机制。来自大量临床和人口研究的证据表明，在出生前暴露于营养供应增加的婴儿在儿童和成人时期超重或肥胖的风险增加。然而，人们并不完全了解为什么会发生这种情况。在正常成年人中，脂肪细胞释放的因子在维持能量平衡方面发挥着重要作用，脂肪细胞或血液循环中这些因子水平的变化会导致体重增加，并导致身体组织对胰岛素等激素的敏感性降低。脂肪细胞在出生前就已发育，因此胎儿营养供给的变化有可能终生改变脂肪细胞的功能特性。在这一建议中，我们将研究胎儿时期暴露于增加的营养供应对出生后脂肪细胞特性的影响，并确定这些变化如何解释这些个体肥胖的发展。了解将肥胖风险与出生前事件联系起来的机制，将使未来的临床医生能够为超重、葡萄糖不耐受或糖尿病母亲所生的孩子提供一个健康的生命开端。

In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This research proposal seeks to define the mechanisms which lead to the development of obesity. Evidence from a large range of clinical and population-based studies has shown that infants who are exposed to an increased supply of nutrients before birth have an increased risk of being overweight or obese as children and adults. It is not however, fully understood why this occurs. In normal adults, factors released by fat cells play an important role in the maintenance of energy balance, and changes in the levels of these factors in the fat cell or in the circulation can lead to increased weight gain and the development of poor sensitivity of the body's tissues to the actions of hormones, such as insulin. Fat cells develop before birth, and therefore changes in nutrient supply to the fetus have the potential to alter the functional properties of fat cells for life. In this proposal, we will investigate the effect of being exposed to an increased supply of nutrients in fetal life on the properties of fat cells after birth and define how such changes explain the development of obesity in these individuals. Understanding the mechanisms which link the risk of obesity to events before birth will allow clinicians of the future to provide children who are born to overweight, glucose-intolerant or diabetic mothers with a healthy start to life.