Leptin Physiology throughout the Life Cycle of the Frog

瘦素是肥胖基因的蛋白质产物，是一种由脂肪细胞分泌的荷尔蒙，对哺乳动物的摄食调节是不可或缺的。瘦素向大脑传递有关长期能量平衡的信息，从而影响生命周期的关键方面，如许多物种的生长和繁殖。此外，近年来发达国家肥胖的流行使人们对瘦素和其他影响食欲和能量代谢的因素产生了浓厚的兴趣。丹佛博士的实验室首次在非哺乳动物物种--非洲爪蛙身上发现了肥胖基因和瘦素的功能特征。到目前为止，除了哺乳动物之外，人们对瘦素的生物学几乎一无所知。这项研究的总体目标是了解瘦素在冷血物种非洲爪哇中的功能，非洲爪哇的血统在2亿多年前与现代哺乳动物的血统背道而驰。青蛙一直是，并将继续是研究动物发育的重要模式生物。运用分子、生理和发育的方法，这项研究要解决的主要问题是：1)瘦素是否在青蛙的长期能量平衡中发挥进化保守的作用，从而影响两栖动物生活史的关键方面，如变态、生长和繁殖？2)青蛙体内何时何地产生瘦素，瘦素的主要作用部位是哪里？3)瘦素是否影响蝌蚪大脑发育，改变蝌蚪的生长和变态的时间？这个项目将为本科生和研究生提供独特的培训机会，为理解这种重要的脊椎动物激素的功能进化提供基础。并建立青蛙作为研究瘦素早期发育作用的模型系统。鉴于全球对人类肥胖症和相关疾病发病率上升的担忧，关于荷尔蒙控制食欲和进食的基础研究尤其及时。

Leptin, the protein product of the obese gene, is a hormone secreted by fat cells that is integral to food intake regulation in mammals. Leptin signals to the brain information about long term energy balance, and thus influences critical aspects of the life cycle such as growth and reproduction in many species. Additionally, the prevalence of obesity in developed countries in recent years has focused intense interest on leptin and other factors that influence appetite and energy metabolism. Dr. Denver's lab reported the first definitive identification of the obese gene and the functional characterization of leptin in a nonmammalian species, the South African clawed frog, Xenopus laevis. Until now, virtually nothing was known about the biology of leptin outside of mammals. The overall goal of this research is to understand the functions of leptin in a cold blooded species, Xenopus laevis, whose lineage diverged from that of modern mammals over 200 million years ago. The frog has been, and continues to be an important model organism for the study of animal development. Using molecular, physiological and developmental approaches, the major questions to be addressed in this research are: 1) Does leptin play an evolutionarily conserved role in long term energy balance in frogs, and thereby influence critical aspects of the amphibian life history such as metamorphosis, growth and reproduction? 2) Where and when in the frog's body is leptin produced, and where are leptin's major sites of action? 3) Does leptin influence tadpole brain development, alter tadpole growth and the timing of metamorphosis?This project, which will offer unique training opportunities for undergraduate and graduate students, will provide a foundation for understanding the functional evolution of this important vertebrate hormone, and establish the frog as a model system for the study of leptin actions in early development. Basic research on the hormonal control of appetite and feeding is particularly timely given the global concern over the rising incidence of obesity and related disorders in humans.