Leptin in neuroendocrine function

瘦素在神经内分泌功能中的作用

• 批准号: 7024982
• 负责人: JEAN Lin CHAN
• 金额: $ 13.03万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7024982
• 关键词: adrenocorticotropic hormone; amenorrhea; bioenergetics; body composition; bone metabolism; clinical research; clinical trials; cortisol; dietary restriction; fasting; gender difference; hormone therapy; human subject; human therapy evaluation; hypothalamic pituitary adrenal axis; insulinlike growth factor; leptin; luteinizing hormone; menstrual cycle; neuroendocrine system; nutrition related tag; obesity; patient oriented research; pituitary gonadal axis; reproductive system disorder chemotherapy; thyrotropin

DESCRIPTION (provided by applicant): This K23 proposal on the role of leptin in neuroendocrine function and the treatment of HA combines a rigorous research agenda, close personal mentoring, and coursework tailored to train Dr. Jean L. Chan as an independent clinical investigator. Dr. Chan is currently a third-year fellow in Endocrinology and Metabolism who has an interest in human leptin physiology and treatment studies and has recently completed the first interventional study to evaluate the role of leptin in the neuroendocrine and immune response to fasting in healthy lean men - a subject of profound physiologic interest with substantial clinical relevance and significance for both high-leptin and low-leptin states. She is also currently enrolled at Harvard Medical School in the Clinical Scholar's program designed to train postdoctoral fellows in clinical investigation. For the K23 proposal, she intends to evaluate whether a threshold level of leptin is of importance in the neuroendocrine response to fasting by studying obese leptin-resistant men and whether gender has an effect on this response by studying women, who have different leptin physiology from men. The study design will involve double-blind, randomized, placebo-controlled fasting studies with leptin administration. This research may elucidate the compensatory neuroendocrine mechanisms responsible for the plateauing effect of caloric restriction in the treatment of obesity and contribute to our understanding of the neuroendocrine abnormalities associated with eating disorders. This proposal will also evaluate leptin as a potential treatment to restore menstrual cycles in women with HA, a low-leptin state associated with abnormalities in GnRH pulsatility as well as other neuroendocrine axes and bone metabolism. Dr. Chan is currently conducting a pilot study to evaluate the feasibility of this hypothesis and will use a larger, placebo-controlled study design with leptin administration for the K23 proposal. Dr. Christos Mantzoros, an established expert and leader in the leptin field, will be Dr. Chan's mentor. The Clinical Scholars program will encompass a thesis-level research effort, and Dr. Chan has assembled a thesis committee who is monitoring and guiding her progress. She will also have the opportunity to take advanced biostatistics classes at Harvard Public Health School. The proposed research will not only provide critically important and novel scientific information in the area of leptin physiology in humans but it will serve as the foundation for developing new avenues of future research.

描述（由申请人提供）： 这项关于瘦素在神经内分泌功能和 HA 治疗中的作用的 K23 提案结合了严格的研究议程、密切的个人指导以及为将 Jean L. Chan 博士培养为独立临床研究者而量身定制的课程。 陈博士目前是内分泌学和代谢学的三年级研究员，他对人类瘦素生理学和治疗研究感兴趣，最近完成了第一项干预研究，以评估瘦素在健康瘦身中对禁食的神经内分泌和免疫反应中的作用男性 - 一个具有深远生理意义的主题，对于高瘦素和低瘦素状态具有重要的临床相关性和意义。 她目前还就读于哈佛医学院的临床学者计划，该计划旨在培训临床研究方面的博士后研究员。 对于 K23 提案，她打算通过研究肥胖的瘦素抵抗男性来评估瘦素的阈值水平在禁食的神经内分泌反应中是否重要，并通过研究具有与瘦素生理学不同的女性来评估性别是否对此反应有影响。男人。 该研究设计将涉及瘦素给药的双盲、随机、安慰剂对照禁食研究。 这项研究可能阐明导致热量限制治疗肥胖症的平台效应的代偿性神经内分泌机制，并有助于我们理解与饮食失调相关的神经内分泌异常。 该提案还将评估瘦素作为恢复 HA 女性月经周期的潜在治疗方法，HA 是一种与 GnRH 搏动异常以及其他神经内分泌轴和骨代谢异常相关的低瘦素状态。 Chan 博士目前正在进行一项试点研究，以评估这一假设的可行性，并将针对 K23 提案使用更大规模的安慰剂对照研究设计，并使用瘦素给药。 Christos Mantzoros 博士是瘦素领域的知名专家和领导者，他将担任陈博士的导师。临床学者计划将包括论文级别的研究工作，陈博士组建了一个论文委员会来监督和指导她的进展。 她还将有机会在哈佛公共卫生学院学习高级生物统计学课程。 拟议的研究不仅将为人类瘦素生理学领域提供极其重要和新颖的科学信息，而且还将为开发未来研究的新途径奠定基础。