权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

摘要