Montague C T, Prins J B, Sanders L, Zhang J, Sewter C P, Digby J, Byrne C D, O'Rahilly S
Department of Medicine, University of Cambridge, England, UK.
Diabetes. 1998 Sep;47(9):1384-91. doi: 10.2337/diabetes.47.9.1384.
Human omental adipocytes display a range of biochemical properties that distinguish them from adipocytes of subcutaneous origin. However, information about site-related gene expression in human fat cells is limited. We have previously demonstrated that leptin mRNA is markedly overexpressed in abdominal subcutaneous (SC) compared with omental (Om) adipocytes. To further investigate depot-specific differences in adipocyte gene expression, we have measured, in paired samples of isolated human adipocytes obtained from SC and Om fat depots, the expression of mRNAs encoding a number of proteins involved in the control of adipocyte metabolism. In contrast to the marked site-related expression of leptin, genes encoding lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and adipsin were not consistently differentially expressed. Of note, a highly significant inverse correlation between adipocyte PPAR-gamma expression and BMI (r = -0.7, P = 0.0005) was found. In parallel experiments, differential display was used in an attempt to identify novel and/or unexpected adipocyte genes that were expressed in a site-related manner. No transcript that was unique to one or another depot was found, but cellular inhibitor of apoptosis protein-2 (cIAP2) mRNA, which has not previously been reported in adipocytes, was expressed at higher levels in Om than SC adipocytes (Om > SC in all eight subjects; mean Om:SC ratio 1.9 +/- 0.2, P < 0.01). Because cIAP2 may be involved in the regulation of TNF-alpha signaling, this raises the possibility that depot-specific differences may exist in the regulation of adipocyte apoptosis. Thus, of the mRNAs examined to date, only leptin and cIAP2 show consistent site-related expression, suggesting that these molecules may have important roles in determining functional properties particular to individual adipose depots. Given the importance of PPAR-gamma in adipocyte development and insulin sensitivity, the inverse correlation between adipocyte PPAR-gamma mRNA levels and adiposity may represent a local regulatory mechanism restraining fat accumulation and/or may be related to the reduction of insulin sensitivity that occurs with increasing fat mass.
人类网膜脂肪细胞具有一系列生化特性，使其有别于皮下来源的脂肪细胞。然而，关于人类脂肪细胞中与部位相关的基因表达信息有限。我们之前已经证明，与网膜（Om）脂肪细胞相比，瘦素mRNA在腹部皮下（SC）脂肪细胞中显著过表达。为了进一步研究脂肪细胞基因表达的部位特异性差异，我们在从SC和Om脂肪库获取的成对分离人类脂肪细胞样本中，测量了编码一些参与脂肪细胞代谢控制的蛋白质的mRNA表达。与瘦素明显的部位相关表达不同，编码脂蛋白脂肪酶（LPL）、激素敏感性脂肪酶（HSL）、过氧化物酶体增殖物激活受体γ（PPAR-γ）、肿瘤坏死因子-α（TNF-α）和脂肪酶的基因并没有持续出现差异表达。值得注意的是，发现脂肪细胞PPAR-γ表达与BMI之间存在高度显著的负相关（r = -0.7，P = 0.0005）。在平行实验中，采用差异显示法试图鉴定以部位相关方式表达的新的和/或意外的脂肪细胞基因。未发现一个库特有的转录本，但细胞凋亡抑制蛋白-2（cIAP2）mRNA（此前未在脂肪细胞中报道）在Om脂肪细胞中的表达水平高于SC脂肪细胞（所有8名受试者中均为Om > SC；平均Om:SC比值为1.9 +/- 0.2，P < 0.01）。由于cIAP2可能参与TNF-α信号传导的调节，这增加了脂肪细胞凋亡调节中可能存在部位特异性差异的可能性。因此，在迄今为止检测的mRNA中，只有瘦素和cIAP2表现出一致的部位相关表达，表明这些分子可能在决定各个脂肪库特有的功能特性方面发挥重要作用。鉴于PPAR-γ在脂肪细胞发育和胰岛素敏感性中的重要性，脂肪细胞PPAR-γ mRNA水平与肥胖之间的负相关可能代表一种限制脂肪积累的局部调节机制，和/或可能与随着脂肪量增加而发生的胰岛素敏感性降低有关。
