Mechanisms by which adipocytes adapt to cool environmental temperatures

脂肪细胞适应凉爽环境温度的机制

基本信息

批准号：
10212377
负责人：
Ormond A MacDougald
金额：
$ 39.62万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-07 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10212377
关键词：
ATP Synthesis Pathway Address Adipocytes Adipose tissue Afferent Neurons Animals Back Behavioral Blood Vessels Body Temperature Brain Brown Fat Calcium Cell physiology Cells Characteristics Chest Complex Creatine Kinase Cultured Cells Data Dermal Diabetes Mellitus Distal Energy Metabolism Exercise Futile Cycling Gene Expression Genetic Genetic Transcription Hour Housing Human Hypothalamic structure Incidence Intervention Knowledge Limb structure Lipids Literature Mammals Marrow Mediating Metabolic Metabolism Mitochondria Modeling Molecular Monounsaturated Fatty Acids Mus Neurons Nutrient Obesity Oxygen Consumption Pathway interactions Peripheral Pharmacology Physiologic Thermoregulation Physiological Physiology Population Property Protons RNA-Binding Proteins Rattus Research Rodent Role Saturated Fatty Acids Series Shivering Signal Transduction Skin Stearoyl-CoA Desaturase Subcutaneous Tissue System Temperature Testing Thermogenesis Triglycerides Unsaturated Fats Visceral Work base cold temperature combat experimental study improved insight lipid metabolism metabolomics neglect novel programs response spine bone structure subcutaneous thermal stress tibia transcriptome sequencing vasoconstriction

项目摘要

Abstract Adipocytes are distributed throughout the body in discrete depots and the intrinsic cellular and metabolic properties of different populations are shaped by the specific niches in which they reside. Whereas visceral adipocytes exist within the body’s core, other subpopulations, including subcutaneous, marrow and dermal adipocytes primarily exist in temperatures well below 37oC. Despite this, the role of environmental temperature has largely been neglected in our consideration of adipocyte molecular and functional characteristics. Hints within historical literature suggest that cooler adipose tissue temperatures are also associated with greater lipid unsaturation. We have found similar correlations in rodents and humans, with cooler distal marrow adipocytes having increased unsaturated lipid composition. Housing rats at thermoneutrality decreases formation of unsaturated lipids in triacylglycerols of marrow adipocytes within the distal tibia and caudal vertebra. Warmer temperature also decreases expression of Stearoyl CoA Desaturase I. Adaptation of cultured adipocytes to 31oC is associated with elevated oxygen consumption, altered nutrient selection, elevated anabolic and catabolic lipid metabolism, and a genetic program for cold-adaptation. We hypothesize that cold adaptation results in profound changes to gene expression and metabolism that allow adipocytes to function at temperatures well below 37oC. To test these hypotheses, we propose a series of specific aims that when successfully completed will provide fundamental insights into how cold-adapted adipocytes are functionally different from their warmer counterparts. These studies will help uncover novel mechanisms of adaptive thermogenesis and identify targets for pharmacologic interventions to increase energy expenditure and combat incidence of obesity and diabetes.

抽象的脂肪细胞分布在整个体内，分别以离散沉积物和内在的细胞和代谢分布不同种群的特性由它们居住的特定壁ni。而内脏脂肪细胞存在于人体的核心内，其他亚群，包括皮下，骨髓和真皮脂肪细胞主要存在于37oC以下的温度中。尽管如此，环境温度的作用在考虑到脂肪细胞分子和功能特征的考虑中，很大程度上被忽略了。提示在历史文献中表明，较冷的脂肪组织温度也与更大的脂质有关不饱和。我们发现啮齿动物和人类的相似性与较冷的远端骨髓脂肪细胞相似不饱和脂质组成增加。恒温的外壳大鼠降低了形成胫骨远端和尾椎骨内三酰基脂肪细胞的三酰基甘油中的不饱和脂质。温暖温度还降低了stearoyl coA去饱和酶的表达。培养的脂肪细胞的适应 31oC与氧气消耗升高，营养选择改变，合成代谢和分解代谢脂质代谢和冷适应的遗传程序。我们假设这种冷适应导致对基因表达和代谢的深刻变化，使脂肪细胞在温度远低于37oC。为了检验这些假设，我们提出了一系列具体目标，成功完成将提供基本的见解与他们的温暖对手不同。这些研究将有助于发现自适应的新机制热生成并确定药物干预措施的目标，以增加能量消耗和战斗肥胖和糖尿病的发生率。