UCP1 in adipose tissues: two steps to full browning
UCP1 in adipose tissues: two steps to full browning
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DOI：
10.1016/j.biochi.2017.01.007
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发表时间：
2017-03-01
期刊：
影响因子：
3.9
通讯作者：
Nedergaard, Jan
中科院分区：
文献类型：
--
作者：
Kalinovich, Anastasia V.;de Jong, Jasper M. A.;Nedergaard, Jan
为了对抗肥胖的发展，可以利用棕色脂肪组织的产热作用来对抗肥胖的发展，这一可能性导致了人们对“褐变剂”的识别产生了极大的兴趣，即增加棕色和褐褐色/米色脂肪组织中UCP1的数量和活性的试剂。然而，当在两个可选步骤中的一个进行分析时，对褐化过程的功能分析得到令人困惑的不同结果。因此，在其中一个步骤中，使用冷驯化作为有效的模型褐变剂，我们发现如果在最初被安置在21℃(最常见的程序)的小鼠中遵循褐化过程，只有微弱的分子证据表明经典的棕色脂肪组织中UCP1基因表达或UCP1蛋白丰度增加；相反，在另一个步骤中，如果从最初饲养在30摄氏度(对小鼠的温度为中性，因此与正常人类条件相似)的小鼠开始，在经典的棕色脂肪组织中观察到UCP1基因表达和UCP1蛋白丰度的大幅增加；当意识到经典的棕色脂肪组织在21℃时已经基本完全分化，从而在进一步的褐变诱导下通过增殖而不是进一步促进细胞分化，这一明显的难题可以得到解决。当分析产热的限制因素，即每个仓库中UCP1蛋白的总量时，经典的棕色脂肪组织是褐化过程的主要部位，无论分析这两个步骤中的哪一个。到目前为止，还没有公开的数据表明，替代褐变剂将选择性地促进褐变/米色组织而不是经典的棕色组织，其程度高于冷驯化。因此，将调查限制在只发生有限部分适应过程的脂肪组织仓库(即褐褐色组织)，并使用不同于成年人通常经历的中温条件的初始条件，可能会严重阻碍对治疗有效的褐变剂的鉴定。因此，这里给出的数据对于分析褐变剂的潜力和人类棕色脂肪组织的性质具有重要的意义。(三)2017年提交人(S)。由Elsevier B.V.出版。这是一篇在CC许可下的开放获取文章
The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps.Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 degrees C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues.Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 degrees C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues.This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed.There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues versus classical brown tissue to a higher degree than does cold acclimation. Thus, to restrict investigations to examine adipose tissue depots where only a limited part of the adaptation process occurs (i.e. the brite/beige tissues) and to use initial conditions different from the thermoneutrality normally experienced by adult humans may seriously hamper the identification of therapeutically valid browning agents. The data presented here have therefore important implications for the analysis of the potential of browning agents and the nature of human brown adipose tissue. (C) 2017 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license