Mechanisms by which adipocytes adapt to cool environmental temperatures

脂肪细胞适应凉爽环境温度的机制

• 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
• 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

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 脂肪细胞以离散的储存库分布在全身各处，并具有内在的细胞和代谢功能 不同种群的特性是由它们所处的特定生态位决定的。而内脏 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37 ℃的温度中。尽管如此，环境温度的作用 在我们考虑脂肪细胞的分子和功能特性时，在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较高的脂质含量有关， 不饱和度我们在啮齿类动物和人类中发现了类似的相关性， 具有增加的不饱和脂质组成。在热中性条件下饲养大鼠可减少 胫骨远端和尾椎内骨髓脂肪细胞三酰甘油中的不饱和脂质。温暖 温度也降低硬脂酰CoA去饱和酶I的表达。培养的脂肪细胞适应 31 ℃与耗氧量升高、营养选择改变、合成代谢升高和 分解代谢脂质代谢，以及适应寒冷的遗传程序。我们假设冷适应 导致基因表达和代谢的深刻变化，使脂肪细胞在 温度远低于37oC。为了验证这些假设，我们提出了一系列具体目标， 成功完成将提供基本的见解如何冷适应脂肪细胞的功能 不同于他们的温暖的同行。这些研究将有助于揭示新的适应机制， 产热和确定药物干预的目标，以增加能量消耗和打击 肥胖和糖尿病的发病率。