Nedergaard Jan, Cannon Barbara
Dept. of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Biochim Biophys Acta. 2013 May;1831(5):943-9. doi: 10.1016/j.bbalip.2013.01.009. Epub 2013 Jan 22.
Because of the possible role of brown adipose tissue and UCP1 in metabolic regulation, even in adult humans, there is presently considerable interest in quantifying, from in-vitro data, the thermogenic capacities of brown and brite/beige adipose tissues. An important issue is therefore to establish which parameters are the most adequate for this. A particularly important issue is the relevance of UCP1 mRNA levels as estimates of the degree of recruitment and of the thermogenic capacity resulting from differences in physiological conditions and from experimental manipulations. By solely following UCP1 mRNA levels in brown adipose tissue, the conclusion would be made that the tissue's highest activation occurs after only 6h in the cold and then successively decreases to being only some 50% elevated after 1month in the cold. However, measurement of total UCP1 protein levels per depot ("mouse") reveals that the maximal thermogenic capacity estimated in this way is reached first after 1month but represents an approx. 10-fold increase in thermogenic capacity. Since this in-vitro measure correlates quantitatively and temporally with the acquisition of nonshivering thermogenesis, this must be considered the most physiologically relevant parameter. Similarly, observations that cold acclimation barely increases UCP1 mRNA levels in classical brown adipose tissue but leads to a 200-fold increase in UCP1 mRNA levels in brite/beige adipose tissue depots may overemphasise the physiological significance of these depots, as the high fold-increases are due to very low initial levels, and the UCP1 mRNA levels reached are at least an order of magnitude lower than in brown adipose tissue; furthermore, based on total UCP1 protein amounts, the brite/beige depots attain only about 10% of the thermogenic capacity of the classical brown adipose tissue depots. Consequently, inadequate conclusions may be reached if UCP1 mRNA levels are used as a proxy for the metabolic significance of recruited versus non-recruited brown adipose tissue and for estimating the metabolic significance of brown versus brite/beige adipose tissues. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.
由于棕色脂肪组织和UCP1在代谢调节中可能发挥的作用，即使在成年人体内，目前人们也非常关注从体外数据中量化棕色脂肪组织和米色脂肪组织的产热能力。因此，一个重要的问题是确定哪些参数最适合于此。一个特别重要的问题是UCP1 mRNA水平作为评估募集程度以及生理条件差异和实验操作导致的产热能力差异的相关性。仅跟踪棕色脂肪组织中的UCP1 mRNA水平，会得出这样的结论：该组织在寒冷环境中仅6小时后就达到最高激活水平，然后在寒冷环境中1个月后逐渐下降至仅升高约50%。然而，测量每个储存部位（“小鼠”）的总UCP1蛋白水平发现，以这种方式估计的最大产热能力在1个月后才首次达到，但代表产热能力增加了约10倍。由于这种体外测量在数量和时间上与非颤抖性产热的获得相关，因此必须将其视为最具生理相关性的参数。同样，冷适应几乎不会增加经典棕色脂肪组织中的UCP1 mRNA水平，但会导致米色脂肪组织储存部位的UCP1 mRNA水平增加200倍，这可能会过度强调这些储存部位的生理意义，因为高倍数增加是由于初始水平非常低，而且达到的UCP1 mRNA水平至少比棕色脂肪组织低一个数量级；此外，基于总UCP1蛋白量，米色脂肪组织储存部位的产热能力仅达到经典棕色脂肪组织储存部位的约10%。因此，如果将UCP1 mRNA水平用作已募集与未募集棕色脂肪组织的代谢意义的替代指标，以及用于估计棕色脂肪组织与米色脂肪组织的代谢意义，可能会得出不恰当的结论。本文是名为“棕色和白色脂肪：从信号传导到疾病”的特刊的一部分。
