Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; and.
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden.
Am J Physiol Endocrinol Metab. 2015 Jun 15;308(12):E1085-105. doi: 10.1152/ajpendo.00023.2015. Epub 2015 Apr 21.
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.
目前，关于人类棕色脂肪组织的性质存在争议：它是经典的棕色脂肪，还是米色/ beige 脂肪。棕色和米色/ beige 脂肪组织具有不同的发育起源和提出的不同功能，因此必须确定人类脂肪库的身份，以便从招募和激活它们治疗肥胖症和 2 型糖尿病的角度出发。为了鉴定这些组织，已经提出了许多标记基因，但这些标记的有效性尚未得到很好的记录。我们使用了已建立的棕色（肩胛间）、米色（腹股沟）和白色（附睾）小鼠脂肪组织及其相应的原代细胞培养物作为验证者，并检查了一系列先前在讨论棕色脂肪组织性质时使用的标记的信息价值。这些标记中的大多数在组织分类方面出人意料地没有提供信息（Car4、Cited1、Ebf3、Eva1、Fbxo31、Fgf21、Lhx8、Hoxc8 和 Hoxc9）。只有 Zic1（棕色）、Cd137、Epsti1、Tbx1、Tmem26（米色）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，米色标记的表达并没有维持。在更广泛的脂肪库中，这些经过验证的标记提供了关于库身份的新信息。主成分分析支持了我们的单基因结论。此外，Zic1、Hoxc8、Hoxc9 和 Tcf21 显示出前后表达模式，表明解剖定位与脂肪组织身份（可能还有功能）之间存在关系。综上所述，这些经过验证的标记基因的观察到的表达模式需要重新考虑小鼠和人类脂肪库的身份。
