Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
Obesity (Silver Spring). 2010 May;18(5):872-878. doi: 10.1038/oby.2009.512. Epub 2010 Jan 28.
We have previously demonstrated that subcutaneous and intra-abdominal adipose tissue show different patterns of expression for developmental genes (Shox2, En1, Tbx15 Hoxa5, Hoxc8, and Hoxc9), and that the expression level of Tbx15 and Hoxa5 in humans correlated with the level of obesity and fat distribution. To further explore the role of these developmental genes in adipose tissue, we have characterized their expression in different adipose depots in mice, and studied their regulation in obesity and by fasting. Developmental and adipogenic gene expression was compared in two subcutaneous and three intra-abdominal white adipose tissue (WAT) depots as well as brown adipose tissue (BAT) from lean or obese mice in a fed or fasting state. Each of these six adipose depots display a unique pattern of developmental gene expression, whereas expression of adipogenic transcription factors PPARgamma2 C/EBPalpha, beta, and Delta showed constant expression levels in all depots. Expression levels of developmental genes were similar in obese (ob/ob and high-fat diet (HFD)) and lean mice in most depots. Fasting systematically decreased expression of Hoxc8, PPARgamma2, and increased C/EBPDelta in both lean and ob/ob mice, but produced only variable changes in the expression of other developmental and adipogenic genes. These data indicate that each fat depot has a unique developmental gene expression signature, which is largely independent of nutritional state. This finding further supports a fundamental role of developmental genes in fat distribution and the development and/or function of specific adipose tissue depots.
我们之前已经证明,皮下和腹部脂肪组织在发育基因(Shox2、En1、Tbx15、Hoxa5、Hoxc8 和 Hoxc9)的表达模式上存在差异,并且人类 Tbx15 和 Hoxa5 的表达水平与肥胖程度和脂肪分布水平相关。为了进一步探索这些发育基因在脂肪组织中的作用,我们已经在小鼠的不同脂肪组织中对其表达进行了特征描述,并研究了它们在肥胖和禁食中的调节作用。在进食或禁食状态下,我们比较了瘦鼠和肥胖鼠(ob/ob 和高脂肪饮食(HFD))的两种皮下和三种腹部白色脂肪组织(WAT)以及棕色脂肪组织(BAT)中的发育和脂肪生成基因表达。这六个脂肪组织中的每一个都表现出独特的发育基因表达模式,而脂肪生成转录因子 PPARgamma2、C/EBPalpha、beta 和 Delta 的表达水平在所有组织中保持恒定。在大多数组织中,肥胖(ob/ob 和 HFD)和瘦鼠的发育基因表达水平相似。禁食在瘦鼠和 ob/ob 鼠中系统性地下调了 Hoxc8、PPARgamma2 的表达,并增加了 C/EBPDelta 的表达,但对其他发育和脂肪生成基因的表达只产生了可变的变化。这些数据表明,每个脂肪组织都有独特的发育基因表达特征,这在很大程度上独立于营养状态。这一发现进一步支持了发育基因在脂肪分布以及特定脂肪组织的发育和/或功能中的基本作用。