Converting More Brown Adipocytes From Resting to Active State

将更多棕色脂肪细胞从静止状态转变为活跃状态

基本信息

批准号：
9014023
负责人：
Qiong Annabel Wang
金额：
$ 11.2万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9014023
关键词：
Adipocytes Adipose tissue Adult Award Biological Biology Brown Fat Burn injury Cell Count Cells Collaborations Complex Data Development Development Plans Developmental Cell Biology Diet Dyslipidemias Effectiveness Embryo Embryonic Development Epidemic Fatty acid glycerol esters Fingerprint Funding Future Genes Goals Heterogeneity Homeostasis Human Hyperlipidemia In Vitro Individual Insulin Resistance Knowledge LacZ Genes Learning Life Style Lipids Manuscripts Mentors Metabolic Metabolic Diseases Metabolic syndrome Metabolism Morphology Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Occupations PPAR gamma Pathogenesis Pharmacologic Substance Physiology Population Prevalence Publishing Rana Regulation Regulatory Pathway Relative (related person)Reporter Research Rest Rewards Rodent Scientist Techniques Temperature Therapeutic Thermogenesis Time Tissue Differentiation Tomatoes Writing adiponectin base career career development cold temperature environmental change feeding improved in vivo insight lipid biosynthesis mouse model novel strategies obesity treatment postnatal prevent programs public health relevance research study skills subcutaneous

项目摘要

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 This application is based on a recent unpublished discovery by Dr.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.

描述（由申请人提供）：研究：近年来的研究表明，棕色脂肪组织活性的增强可以纠正高脂血症并预防饮食引起的肥胖及其有害的代谢后果。人们普遍认为所有“经典”棕色脂肪细胞都是棕色的。该应用基于王博士最近未发表的一项发现，即正常棕色脂肪中共存着两种新的、不同的“经典”棕色脂肪细胞群，它们表现出不同的转录指纹和假设它们是“活跃的”高产热棕色脂肪细胞和“静止的”低产热棕色脂肪细胞。该项目将探索这两种棕色脂肪细胞亚群在发育过程中以及在寒冷等环境和生理学挑战下的功能、动态和调节。通过弄清楚导致棕色脂肪细胞两个亚群之间多样性的关键调控途径，我们可以确定诱导棕色脂肪细胞从低产热能力向高产热能力相互转化的潜在药物靶标。同时，拟议的研究还将调查两个亚群在成熟过程中何时发生变化；以及高脂肪饮食挑战如何损害两个亚群的相互转化。总而言之，拟议的研究将揭示棕色的复杂生理学。脂肪组织，这对于提高我们确定针对肥胖和 II 型糖尿病的潜在最有效治疗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的富有成效的学术实验室，致力于新陈代谢。研究重点是肥胖、2 型糖尿病和相关代谢综合征的发病机制和治疗。为了能够建立自己的独立研究计划，她在奖励期内的近期职业目标是： 1) 学习该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知识，这与她目前的导师不同。 3) 通过发表更多研究文章，进一步练习写作和发表手稿的技能。同事寻找可能适合的工作5) 为我未来的资助申请建立独立的资助记录：在获奖期间，王将通过与她的 Philipp Scherer 博士和导师合作者的不断互动，加强她在上述关键职业目标方面的有效性。 Sean Morrison 博士、Ralph DeBerardinis 博士和 Rana Gupta 博士还将完成 UTSW 提供的几门课程，为她的独立做好准备。