A stringent validation of mouse adipose tissue identity markers
A stringent validation of mouse adipose tissue identity markers
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DOI：
10.1152/ajpendo.00023.2015
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发表时间：
2015-06-15
影响因子：
5.1
通讯作者：
Nedergaard, Jan
中科院分区：
文献类型：
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作者：
de Jong, Jasper M. A.;Larsson, Ola;Nedergaard, Jan
人类棕色脂肪组织的性质目前存在争议：它是经典棕色还是浅褐色。棕色和白色/米色组织不同的发育起源和提出的不同功能使得从招募和激活它们治疗肥胖和2型糖尿病的角度确定人类仓库的身份至关重要。为了鉴定组织，已经提出了一些标记基因，但这些标记的有效性尚未得到很好的记录。我们使用已建立的棕色（肩胛间）、白色（腹股沟）和白色（附睾）小鼠脂肪组织和相应的原代细胞培养作为验证物，并检查了先前讨论中使用的一系列建议标记的信息价值，考虑到人类棕色脂肪组织的性质。出乎意料的是，这些标记中的大多数在组织分类方面没有信息（Car4、Cited1、Ebf3、Eva1、Fbxo31、Fgf21、Lhx8、Hoxc8和Hoxc9）。只有Zic1（棕色）、Cd137、Epsti1、Tbx1、Tmem26（白色）和Tcf21（白色）在这三种组织中被证明是有信息的。然而，在细胞培养中，brite标记的表达不能维持。在更广泛的脂肪库中，这些经过验证的标记提供了关于脂肪库身份的新信息。主成分分析支持我们的单基因结论。此外，Zic1、Hoxc8、Hoxc9和Tcf21呈现正向表达模式，表明解剖定位与脂肪组织身份（以及可能的功能）之间存在关系。总之，观察到的这些经过验证的标记基因的表达模式需要重新考虑小鼠和人类的脂肪储存身份。
The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification (Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.