LEPTIN STRUCTURE AND FUNCTION IN GREEN SUNFISH

肥胖是一个严重的人类健康问题，它往往会增加其他疾病的发病率，如心脏病，中风，糖尿病，甚至癌症。因此，了解肥胖的细胞和分子基础无疑将带来巨大的人类健康益处。最近，一种激素（瘦素，或ob）被描述为在哺乳动物中充当“脂肪”;感知身体的肥胖并调节食欲和新陈代谢以维持恒定的脂肪储存。瘦素有可能解释脂质功能的许多方面（包括人类肥胖），正因为如此，它一直是过去五年来密集研究的焦点。几乎完全是，研究工作，以了解瘦素功能使用哺乳动物模型，大概是由于明显的适用性，以人类。我们断言，比较的方法（例如，研究瘦素功能在进化上遥远的模式生物）在了解瘦素功能的效用。比较的方法已成功地应用于其他生理问题，解决问题，不容易接近与哺乳动物模型（即肌红蛋白功能）。我们有第一个数据表明瘦素存在于鱼类，我们认为，鱼类瘦素的实验可能揭示瘦素功能的独特方面在所有脊椎动物。拟议的实验旨在了解瘦素的生理作用，并确定其在硬骨鱼（蓝鳃太阳鱼，绿色太阳鱼）的一级结构。所提出的研究结果将1）确定瘦素对鱼类代谢燃料分配的影响，以及2）通过比较序列分析鉴定瘦素的潜在功能结构域。

Obesity is a serious human health problem that often increases the incidence of other diseases, such as heart disease, stroke, diabetes, and even cancer. Understanding the cellular and molecular underpinnings of obesity will therefore undoubtedly lead to a substantial human health benefits. Recently, a hormone (leptin, or ob) was described in mammals that acts as a "lipostat"; sensing the body's adiposity and regulating appetite and metabolism to maintain constant fat stores. Leptin has the potential to explain many aspects of lipid function (including human obesity), and because of this it has been the focus of intense research effort over the past five years. Almost exclusively, the research effort to understand leptin function has used mammalian models, presumably due to the obvious applicability to humans. We assert that a comparative approach (e.g. studying leptin function in evolutionarily distant model- organisms) has utility in understanding leptin function. The comparative approach has been successfully applied to other physiological questions, solving problems not easily approached with mammalian models (i.e. myoglobin function). We have the first data that point to leptin's existence in.fishes, and we submit that experiments with fish leptin may uncover unique aspects of leptin function in all vertebrates. The proposed experiments are designed to understand the physiological effects of leptin, and determine its primary structure in a bony fish (Lepomis cyanellus, the green sunfish). Results of the proposed research will l) determine the effect of leptin on metabolic fuel partitioning in fish and 2) identify potential function domains in leptin via comparative sequence analysis.