Metabolic basis of thermogenesis in cold exposed humans

产热的增加是通过运动自愿实现的，或通过激活非颤抖性产热（NST）和颤抖性产热（ST）非自愿实现的。当运动不可能时，NST和ST的激活对于维持核心温度至关重要。对新生儿的研究表明，NST与大的浅表和深棕色脂肪组织（BAT）库的激活有关。虽然很明显，NST是冷暴露的婴儿产热的一种重要手段，但这一途径在成人中的确切作用仍存在争议。然而，最近的证据清楚地表明，成年人仍然保留着大量的BAT。BAT的数量和代谢活动在个体之间差异很大。鉴于最近证明人类存在BAT代谢活动，这一现象引起了基础和健康研究人员的关注，需要重新审视。因此，本提案的目的是测量冷暴露和冷适应对成年人产热和组织特异性代谢的影响。为了实现这一目标，必须实现三个短期目标：我们将1）确定全身和组织特异性葡萄糖和脂肪酸摄取，2）量化BAT激活对ST反应的影响，3）确定冷适应变化对BAT激活、能量代谢和ST活性的影响。研究将基于作为我们先前工作的一部分而开发的实验范式，该工作主要针对热，代谢和电生理的量化。全身代谢反应将通过全身间接量热法和同位素方法确定，而组织特异性代谢将使用PET/CT测量。 拟议的研究将为通过饮食和/或身体干预制定战略提供基础，以提高在寒冷中的生存机会。这对于许多体育活动以及工业和军事应用特别相关。拟议的调查只是BAT代谢更广泛研究计划的必要的第一步。

The increase in heat production is achieved voluntarily through exercise or involuntarily by the activation of non-shivering thermogenesis (NST) and shivering thermogenesis (ST). When exercise is not possible, activation of NST and ST is essential for maintaining core temperature. Research in newborn humans has shown that NST is associated with the activation of large superficial and deep brown adipose tissue (BAT) depots. While it is clear that NST is an essential means of thermogenesis in cold-exposed infants, the exact contribution of this pathway in adults remains controversial. However, recent evidence has clearly shown that adult humans still retain significant amounts of BAT. Both quantity and metabolic activity of BAT are highly variable among individuals. In view of the very recent demonstration of the presence of BAT metabolic activity in humans, this phenomenon has attracted the attention of fundamental and health researchers alike and needs to be revisited. Therefore, the purpose of this proposal is to measure the effects of cold-exposure and cold-acclimation on thermogenesis and tissues-specific metabolism in adult humans. To achieve this goal, three short-term objectives must be carried out: we will 1) determine whole-body and tissue-specific glucose and fatty acid uptake, 2) quantify the effect of BAT activation on ST responses and, 3) determine the effects of cold-acclimation changes in BAT activation, energy metabolism and ST activity. Studies will be based on an experimental paradigm developed as part of our previous work which has been primarily directed to the quantification of thermal, metabolic and electrophysiological. Whole-body metabolic responses will be determined by whole-body indirect calorimetry and isotopic methodologies whereas tissue-specific metabolism will be measured using PET/CT. The proposed studies will provide building blocks for developing strategies through dietary and/or physical interventions to improve chances of survival in the cold. This is particularly relevant for many athletic activities as well as industrial and military applications. The proposed investigations are but the necessary first step of a broader research program on BAT metabolism.