Doctoral Dissertation Improvement: Conceptualizing the Adaptive Significance of Brown Adipose Tissue in Cold Climates

博士论文改进：概念化棕色脂肪组织在寒冷气候下的适应性意义

• 批准号: 1455804
• 负责人: William Leonard
• 金额: $ 2.52万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455804&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Conceptualizing; Adaptive

Arctic regions present extreme environmental stresses, such as severe cold and low biodiversity; yet, human populations have managed to survive in these territories for thousands of years. As human populations migrated into high-latitude regions, they underwent an adaptive shift that included cultural, behavioral and biological dimensions. Contemporary circumpolar populations appear to adapt to cold temperatures physiologically by generating high metabolic rates; however, the mechanisms that control this biological adaptation are poorly understood. Brown adipose tissue (BAT), a special type of fat that is highly metabolically active, has been recognized for decades as the primary source of heat production among infants. However, it was previously assumed that as humans develop, BAT levels decrease to trace amounts. Within recent years, BAT has been discovered to be present and active among many adults. Furthermore, due its ability to convert stored fats and sugars into heat, the presence of BAT may have protective effects against obesity. It is not known why some adults have BAT while others do not, and whether BAT activity is adaptive against cold temperatures. This project will examine variation in BAT activity among indigenous and non-indigenous populations living in cold climates to enhance our understanding of biological adaptations to cold; early-life factors that may shape adult metabolism; and population variation in metabolic disease risk. In addition, the project will support training of a female graduate student in the STEM sciences, foster research collaborations, and provide a new, portable method for quantifying fat metabolic activity. An elevated resting metabolic rate (RMR) and efficient non-shivering thermogenesis (NST) are central biological adaptations to cold climates, but the mechanisms that dictate these metabolic adaptations are poorly understood. Researchers have recently discovered that brown adipose tissue (BAT), a form of fat that is highly thermogenic, is present among adults. This study investigates multiple levels of adaptation to cold stress by testing hypotheses regarding variation in adult BAT heat production. The proposed one-year study will compare groups living in Siberia that have been exposed to cold stress over various time depths. BAT activity will be quantified using infrared thermal imaging of the neck and shoulders. RMR will be measured using indirect calorimetry. Participants will wear temperature loggers for 72 hours to quantify average daily cold exposure. Anthropometric measurements will be taken using standardized techniques. Finally, a modified survey will be used to collect data on lifestyle, socioeconomic status and early-life cold exposure.

北极地区存在极端的环境压力，例如严寒和生物多样性低;然而，人类已经在这些地区生存了数千年。随着人口迁移到高纬度地区，他们经历了包括文化，行为和生物层面的适应性转变。当代环极人群似乎通过产生高代谢率在生理上适应寒冷的温度;然而，控制这种生物适应的机制却知之甚少。棕色脂肪组织（BAT）是一种具有高度代谢活性的特殊脂肪，几十年来一直被认为是婴儿产热的主要来源。 然而，以前的假设是，随着人类的发展，BAT水平下降到痕量。近年来，人们发现BAT在许多成年人中存在并活跃。此外，由于其将储存的脂肪和糖转化为热量的能力，BAT的存在可能对肥胖有保护作用。目前尚不清楚为什么有些成年人有BAT而另一些没有，以及BAT活动是否适应寒冷的温度。该项目将研究生活在寒冷气候中的土著和非土著人口中BAT活动的变化，以提高我们对寒冷的生物适应性的理解;可能影响成年人新陈代谢的早期因素;以及代谢疾病风险的人口变化。此外，该项目还将支持STEM科学女研究生的培训，促进研究合作，并提供一种新的便携式方法来量化脂肪代谢活动。升高的静息代谢率（RMR）和有效的非颤抖性产热（NST）是生物适应寒冷气候的核心，但决定这些代谢适应的机制知之甚少。研究人员最近发现，棕色脂肪组织（BAT），一种高度产热的脂肪形式，存在于成年人中。本研究通过测试关于成年BAT产热变化的假设，调查了对冷应激的多个适应水平。这项为期一年的研究将比较生活在西伯利亚的群体，这些群体在不同的时间深度受到寒冷的压力。BAT活动将使用颈部和肩部的红外热成像进行量化。将使用间接量热法测量RMR。参与者将佩戴温度记录仪72小时，以量化平均每日寒冷暴露。将使用标准化技术进行人体测量。最后，将使用修改后的调查来收集生活方式，社会经济状况和早期寒冷暴露的数据。