Converting More Brown Adipocytes From Resting to Active State

 描述(申请人提供)：研究：近年来的研究表明，增强棕色脂肪组织的活性可以纠正高脂血症，防止饮食诱导的肥胖及其有害的代谢后果。人们普遍认为，棕色脂肪中的所有“经典”棕色脂肪细胞在功能上是相似的。这一应用是基于王博士最近未发表的一项发现，即在正常的棕色脂肪中共存着两个新的、不同的“经典”棕色脂肪细胞群体，它们显示出不同的转录指纹和形态。假设它们是“活跃的”高生热的，而“静止的”低生热的棕色脂肪细胞。本项目将探索这两个棕色脂肪细胞亚群在发育过程中以及在寒冷暴露和高脂饮食等环境和生理挑战下的功能、动态和调节。通过找出导致棕色脂肪细胞亚群差异的关键调控途径，我们可以确定潜在的药物靶点，诱导棕色脂肪细胞从低产热能力向高产热能力的相互转化。同时，这项拟议的研究还将调查这两个亚群在成熟过程中何时发生差异；以及高脂饮食挑战如何损害这两个亚群的相互转化。总之，这项拟议的研究将揭示棕色脂肪组织的复杂生理学，这对于提高我们识别潜在的最有效的治疗肥胖症和II型糖尿病方法的能力至关重要。职业目标：作为一名生物科学家，王博士的最终职业目标是拥有自己富有成效的学术实验室，致力于代谢研究，专注于肥胖症、2型糖尿病和相关代谢综合征的发病机制和治疗。为了能够建立她的独立研究计划，她在奖励期的直接职业目标是：1)学习发育和细胞生物学领域的新技术和知识。2)获得发育和细胞生物学方面的新知识和专业技能，这一方向与她目前的导师不同。3)通过发表更多的研究文章，进一步练就撰写和发表稿件的技能。4)扩大她的同事网络，寻找合适的工作机会和未来的合作机会。5)为我未来的资助申请建立独立的资助记录。职业发展计划：在获奖期间，王雪红将通过与她的导师菲利普·谢勒博士以及合作者肖恩·莫里森博士、拉尔夫·德贝拉迪尼斯博士和拉娜·古普塔博士的持续互动，加强她在上述关键职业目标方面的有效性。她还将完成UTSW提供的几个课程，为独立做好准备。

 DESCRIPTION (provided by applicant): Research: Studies over recent years revealed that an enhancement of brown adipose tissue activity can correct hyperlipidemia and prevent diet induced obesity and its harmful metabolic consequences. It has widely been assumed that all "classical" brown adipocytes in brown fat were functionally similar. This application is based on a recent unpublished discovery by Dr. Wang that there are two new, distinct, populations of "classical" brown adipocytes co-existing in normal brown fat that display distinct transcriptional fingerprints and morphology. The hypothesis is that they are "active" highly thermogenic and the "resting" low thermogenic brown adipocytes. This project will explore the function, dynamic and regulation of this two brown adipocyte subpopulations during development and under environmental and physiology challenges such as cold exposure and high fat diet feeding. By figuring out the key regulatory pathways leading to the diversity between the two subpopulations of brown adipocytes, we can identify the potential pharmaceutical targets to induce inter-conversion of brown adipocytes from low thermogenic capability to high thermogenic capability. Meanwhile, the proposed research will also investigate when the two subpopulations diverse during maturation; as well as how high fat diet challenge impairs the inter-conversion of the two subpopulations. In summary, the proposed research will unmask the complex physiology of brown adipose tissue, which is essential to improve our ability to identify the potential most effective therapeutic approaches against obesity and type II diabetes. Career goals: Dr. Wang's ultimate career goal as a biological scientist is to have her own productive academic lab devoted to metabolism research focusing on the pathogenesis and treatment of obesity, type 2 diabetes and the related metabolic syndromes. To be able to establish her independent research program, her immediate career objectives in the reward period are to: 1) Learn new techniques and knowledge in the field of developmental and cell biology. 2) Acquire new knowledge and expertise in developmental and cell biology, a direction different from her current mentor. 3) Further practice the skills for writing and publishing manuscripts by publishing more research articles. 4) Expand her network of colleagues for potential well-suited job offers and future collaborations. 5) Establish an independent funding record for my future funding applications. Career development plan: During the award period, Wang will strengthen her effectiveness in the above key career objectives through constant interactions with her mentor Dr. Philipp Scherer and collaborators Drs. Sean Morrison, Ralph DeBerardinis and Rana Gupta. She will also complete several courses provided by UTSW to prepare her for the independence.