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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：
10627980
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/10627980
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 Literature Mammals Marrow Mediating Metabolic Metabolism Mitochondria Modeling Molecular Monounsaturated Fatty Acids Mus Neurons Nutrient Obesity Oxygen Consumption Pathway interactions Peripheral Physiologic Thermoregulation Physiological Physiology Population Property Protons RNA-Binding Proteins Rattus Research Rodent Role Saturated Fatty Acids Series Shapes Shivering Signal Transduction Skin Stearoyl-CoA Desaturase Subcutaneous Tissue System Temperature Testing Thermogenesis Triglycerides Unsaturated Fats Visceral Work cold temperature combat experimental study improved insight lipid metabolism metabolomics neglect novel pharmacologic posttranscriptional 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身体的离散库中，并且内在的细胞和代谢不同人群的特性是由他们居住的特定生态位决定的。而本能的脂肪细胞存在于身体的核心、其他亚群，包括皮下、骨髓和真皮脂肪细胞主要存在于远低于 37oC 的温度下。尽管如此，环境温度的作用在我们对脂肪细胞分子和功能特征的考虑中很大程度上被忽视了。提示历史文献表明，较低的脂肪组织温度也与较高的脂质有关不饱和度。我们在啮齿动物和人类中发现了类似的相关性，远端骨髓脂肪细胞温度较低具有增加的不饱和脂质成分。将大鼠饲养在热中性环境中可减少远端胫骨和尾椎内骨髓脂肪细胞三酰甘油中的不饱和脂质。更温暖温度也会降低硬脂酰辅酶 A 去饱和酶 I 的表达。培养的脂肪细胞对 31oC 与耗氧量增加、营养选择改变、合成代谢和代谢水平升高有关分解代谢脂质代谢和冷适应遗传程序。我们假设冷适应导致基因表达和代谢发生深刻变化，使脂肪细胞能够在温度远低于 37oC。为了检验这些假设，我们提出了一系列具体目标，当成功完成将为了解冷适应脂肪细胞的功能提供基础见解与温暖的同行不同。这些研究将有助于揭示适应性的新机制生热作用并确定药物干预的目标，以增加能量消耗和对抗肥胖和糖尿病的发生率。