Sato Takashige, Nagafuku Masakazu, Shimizu Kyoko, Taira Toshio, Igarashi Yasuyuki, Inokuchi Jin-ichi
Faculty of Pharmaceutical Sciences, Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Japan.
Cell Biol Int. 2008 Nov;32(11):1397-404. doi: 10.1016/j.cellbi.2008.08.010. Epub 2008 Aug 20.
Visceral adipose tissue, particularly mesenteric adipose tissue, is important in the pathogenesis of metabolic syndrome. Here, we present a physiologically relevant differentiation system of rat mesenteric-stromal vascular cells (mSVC) to mesenteric-visceral adipocytes (mVAC). We optimized the insulin concentration at levels comparable to those in vivo ( approximately 0.85 ng/ml) by including physiological concentrations of IGF-1. We found that the insulin-like growth factor (IGF-1) and insulin worked synergistically, since IGF-1 alone could induce CCAAT/enhancer binding protein alpha (C/EBPalpha) and adipocyte lipid binding protein (aP2) mRNA expression but not lipid droplet accumulation associated with maturation. Using real-time PCR analyses on 180 adipocyte-related genes, we identified a dramatic effect by IGF-1 plus insulin. We also demonstrated the state of insulin resistance at pathologically high insulin concentrations. This culture system will contribute to understanding the physiological differentiation process and the patho/physiology of mVAC.
内脏脂肪组织，尤其是肠系膜脂肪组织，在代谢综合征的发病机制中起着重要作用。在此，我们展示了一种将大鼠肠系膜基质血管细胞（mSVC）生理相关地分化为肠系膜内脏脂肪细胞（mVAC）的系统。我们通过纳入生理浓度的胰岛素样生长因子1（IGF-1），将胰岛素浓度优化至与体内水平相当（约0.85纳克/毫升）。我们发现胰岛素样生长因子（IGF-1）和胰岛素协同作用，因为单独的IGF-1可诱导CCAAT/增强子结合蛋白α（C/EBPα）和脂肪细胞脂质结合蛋白（aP2）的mRNA表达，但不会诱导与成熟相关的脂滴积累。通过对180个脂肪细胞相关基因进行实时聚合酶链反应（PCR）分析，我们确定了IGF-1加胰岛素具有显著作用。我们还证明了在病理高胰岛素浓度下的胰岛素抵抗状态。这种培养系统将有助于理解mVAC的生理分化过程以及病理/生理学。
