Brown fat dynamics: elucidation of molecular drivers using hibernation as a model

棕色脂肪动力学：以冬眠为模型阐明分子驱动因素

基本信息

批准号：
8442923
负责人：
SANDRA L MARTIN
金额：
$ 14.61万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8442923
关键词：
Abbreviations Animals Atrophic Biological Models Body Temperature Body Weight decreased Body fat Body mass index Brown Fat Calories Data Energy Intake Equilibrium Fluorescent Dyes Foundations Future Gel Gene Expression Profile Goals Health Heating Hibernation Homeostasis Human Hypertrophy Label Liquid Chromatography Mass Spectrum Analysis Metabolic Metabolism Methods Modeling Molecular Names Obesity Organ Pathway interactions Pattern Peptides Phase Phenotype Physiological Post-Translational Protein Processing Preparation Proteins Proteome Public Health RNA Recruitment Activity Regulation Regulatory Pathway Seasons Spermophilus Staging Temperature Thermogenesis Time Tissue Banking Tissue Banks Tissue Extracts Tissues Work base falls gel electrophoresis insight novel novel strategies public health relevance research study segregation tandem mass spectrometry two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Project Summary Obesity is a significant and growing public health problem. It results from loss of energy homeostasis when increases in caloric intake are not balanced by elevated metabolic activity. Brown adipose tissue (BAT) is a potential anti-obesity organ because it is specialized to dissipate energy as heat. Circannual hibernators including ground squirrels naturally challenge conventional views of energy homeostasis by cycling between dramatic extremes of body fat storage and utilization. These animals undergo hypertrophy of BAT each year as they prepare for winter hibernation, and depend on tightly-regulated periods of non-shivering thermogenesis throughout winter hibernation. After spring emergence, BAT nearly disappears but it is re- established each fall in preparation for the next hibernation season. These temporal and functional segregations provide an extraordinary opportunity to examine and define regulatory mechanisms controlling BAT recruitment and activity. We hypothesize that hibernators employ typical mammalian mechanisms for increasing and maintaining BAT, as well as for modulating its activity. Importantly, because of the dynamics and demands of hibernation, hibernators also provide an exceptional, highly-elaborated model system in which to elucidate those mechanisms. The specific goals of the work proposed in this R21 application are to exploit an existing tissue bank, collected from a precisely-timed set of animals representing key points in the phenotypic transitions of a hibernator's year, to first: interrogate the proteome and second: the transcriptome, for qualitative and quantitative changes associated with BAT transitions. This characterization, enabled by unique advantages offered by the hibernating phenotype, will form a necessary foundation for future mechanistic studies of pathways that underlie the regulation of BAT recruitment and the reversible control of its activity, and ultimately to harness them as targets for obesity therapy.

描述（由申请人提供）：项目摘要肥胖是一个重大且日益严重的公共卫生问题。当热量摄入量增加时，能量稳态的丧失无法通过代谢活性升高而平衡。棕色脂肪组织（BAT）是一种潜在的抗肥胖器官将能量作为热量消散。包括地松鼠在内的循环冬眠自然可以通过循环体内脂肪的巨大极端储存和利用方式来挑战传统的能量体内平衡观点。这些动物每年为冬季冬眠做准备时，每年都会发生肥大，并依赖于整个冬季冬眠的严格调节的不动震动。春季出现后，蝙蝠几乎消失了，但每年都会为下一个冬眠季节做准备。这些时间和功能隔离为检查和定义控制BAT募集和活动的调节机制提供了一个非凡的机会。我们假设Hibernators采用典型的哺乳动物机制来增加和维持BAT以及调节其活性。重要的是，由于冬眠的动态和需求，冬眠还提供了一个非凡的，高度生产的模型系统，以阐明这些机制。在本R21应用程序中提出的工作的具体目标是利用现有的组织库，该组织是从冬眠年份表型过渡中的一组精确定时的动物中收集的，首先：询问蛋白质组和第二：转录组，用于与BAT转型相关的定性和定量变化。这种特征是由冬眠表型提供的独特优势来实现的，将为未来的途径机械研究构成必要的基础，这些途径是对BAT募集的调节及其活性的可逆控制，并最终将其作为肥胖症治疗的目标。