LEPTIN STRUCTURE AND FUNCTION IN GREEN SUNFISH

肥胖是一个严重的人类健康问题，通常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会给人类健康带来实质性的好处。最近，一种荷尔蒙(瘦素，或称ob)在哺乳动物中被描述出来，它起到了“lipostat”的作用；感知身体的肥胖，调节食欲和新陈代谢，以维持持续的脂肪储存。瘦素有可能解释脂肪功能的许多方面(包括人类肥胖)，正因为如此，它在过去五年里一直是密集研究的重点。了解瘦素功能的研究几乎完全使用了哺乳动物模型，想必是因为它显然适用于人类。我们断言，一种比较的方法(例如，在进化上遥远的模式生物中研究瘦素的功能)对于理解瘦素的功能是有用的。这种比较方法已经成功地应用于其他生理学问题，解决了用哺乳动物模型不易解决的问题(即肌红蛋白功能)。我们有第一个数据表明瘦素存在于鱼类中，我们提出，对鱼类瘦素的实验可能会揭示所有脊椎动物瘦素功能的独特方面。拟议的实验旨在了解瘦素的生理作用，并确定其在多骨鱼(绿色太阳鱼)中的初级结构。拟议的研究结果将包括：1)确定瘦素对鱼类体内代谢燃料分配的影响；2)通过比较序列分析确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.