Department of Biochemistry/Stem Cell Research, National Institute of Nutrition (Indian Council of Medical Research), Jamai-Osmania, Hyderabad 500007, Andhra Pradesh, India.
Mol Cell Biochem. 2011 Nov;357(1-2):217-25. doi: 10.1007/s11010-011-0892-4. Epub 2011 Jun 2.
Adipose tissue development is a highly regulated phenomenon orchestrated by several check points (recruitment of mesenchymal stem cells and their lineage commitment) to form mature adipocytes. Once committed to obesity, expansion of adipose tissue occurs either by hypertrophy or hyperplasia or by both resulting in an altered physiological status. This precipitates as inflammatory responses, leading to endoplasmic reticulum and oxidative stress altering the gene expression of adipose tissue in a depot-specific manner. However, such studies reporting a phased gene expression profile in conditions of rodent obesity are not reported so far. WNIN/Ob mutant obese rat, developed at our institute is an excellent model to study the pathophysiological changes underlying obesity. Here, we report the gene expression profile of this mutant rat (obese and lean), compared with the parental control, with reference to markers of embryonic stem cells, adipogenesis, inflammation, and senescence in both subcutaneous (SCAT) and retroperitoneal (RPAT) adipose depots representing abdominal fat. We demonstrate an upregulation of genes such as Sox-2, Pref-1, PPARγ2, LPL, IRS-1, GLUT-4, IL-6, TNFα, and telomerase in SCAT and RPAT depots of the obese rat compared to its lean counterpart indicating no difference in fat depots at different locations. This is suggestive of a similar phenotypic expression of mutant gene. Data form the phased gene expression changes of adipogenesis (embryonic/adipogenic/inflammatory) in the present obese rat model system advocate for inflammatory mediated response(s) associated with obesity-a condition often seen in humans.
脂肪组织的发育是一个高度受调控的现象,由几个检查点(间充质干细胞的募集及其谱系承诺)协调,以形成成熟的脂肪细胞。一旦肥胖,脂肪组织的扩张要么通过肥大,要么通过增生,或者两者兼而有之,导致生理状态的改变。这会引发炎症反应,导致内质网和氧化应激以特定脂肪库的方式改变脂肪组织的基因表达。然而,到目前为止,还没有报道在肥胖啮齿动物的情况下报告分阶段基因表达谱的研究。我们研究所开发的 WNIN/Ob 肥胖突变大鼠是研究肥胖症潜在病理生理变化的优秀模型。在这里,我们报告了这种突变大鼠(肥胖和瘦)的基因表达谱,与亲本对照相比,参照胚胎干细胞、脂肪生成、炎症和衰老的标志物,在皮下(SCAT)和腹膜后(RPAT)脂肪库中,代表腹部脂肪。我们证明了肥胖大鼠的 SCAT 和 RPAT 脂肪库中 Sox-2、Pref-1、PPARγ2、LPL、IRS-1、GLUT-4、IL-6、TNFα 和端粒酶等基因的上调,表明不同部位的脂肪库没有差异。这表明突变基因的表型表达相似。本肥胖大鼠模型系统中脂肪生成(胚胎/脂肪/炎症)分阶段基因表达变化的数据表明,肥胖与炎症介导的反应有关,这种情况在人类中很常见。