Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, c/Irunlarrea 1, Pamplona, Spain.
J Physiol Biochem. 2011 Sep;67(3):453-61. doi: 10.1007/s13105-011-0081-7. Epub 2011 Mar 11.
Thrombospondin 1 (TSP-1), an antiangiogenic factor and transforming growth factor (TGF)-β activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow or a high-fat diet (HFD) for 50 days were isolated and incubated (24-72 h) in low (5.6 mM) or high (HG; 25 mM) glucose, in the presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulin-resistant adipocytes. The difference between expression and secretion patterns suggests a posttranscriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.
血小板反应蛋白 1（TSP-1）是一种抗血管生成因子和转化生长因子（TGF）-β活性调节剂，最近被认为是一种与肥胖、炎症和胰岛素抵抗过程相关的脂肪因子。在本研究中，用标准饲料或高脂肪饮食（HFD）喂养 50 天的大鼠的附睾脂肪细胞被分离出来，并在低（5.6mM）或高（HG；25mM）葡萄糖中孵育（24-72 小时），同时存在或不存在 1.6nM 胰岛素。用 HFD 喂养的大鼠表现出明确的肥胖状态。HFD 大鼠血清 TSP-1 水平和 TSP-1 基础表达高于对照组。与对照组相比，HFD 动物的脂肪细胞表现出胰岛素抵抗状态，这表明胰岛素刺激的葡萄糖摄取较低。肥胖动物的脂肪细胞在 24 小时时 TSP-1 表达更高，但当用 HG 处理脂肪细胞时，这些表达水平急剧下降。之后在 72 小时时，HFD 大鼠脂肪细胞中的 TSP-1 表达较低，而其他处理则没有影响。令人惊讶的是，在两种类型的脂肪细胞中，HG 处理在 72 小时时显著增加了这种蛋白质的分泌水平，尽管在肥胖动物的脂肪细胞中更高。最后，HG 处理显著降低了两种类型脂肪细胞的细胞活力。总之，在胰岛素抵抗脂肪细胞的体外模型中，TSP-1 的表达/分泌受到了调节。表达和分泌模式的差异表明存在转录后调节。本研究证实 TPS-1 与肥胖相关机制密切相关。
