Morin C L, Pagliassotti M J, Windmiller D, Eckel R H
Division of Endocrinology, Metabolism, and Diabetes, University of Colorado, Denver, USA.
J Gerontol A Biol Sci Med Sci. 1997 Jul;52(4):B190-5. doi: 10.1093/gerona/52a.4.b190.
High levels of adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) mRNA and protein have previously been associated with genetic models of obesity and insulin resistance. Because there are endogenous TNF inhibitors it is unknown if AT-TNF activity is also increased. We hypothesized that AT-TNF activity would increase in older animals because of an accumulation of fat mass. We chose to study 2 different-aged male Fischer 344 rats, 3-month-old (young) and 14-month-old (mature) because fat mass should be quite different but insulin action on glucose metabolism similar. Indeed, mature rats had over 1.5-fold more fat mass, but whole body insulin resistance, as estimated by fasting plasma insulin, was similar to young rats. Mature rats had twice as much AT-TNF activity as the young in both the epididymal (EPI) and retroperitoneal (Retro) fat pads (p < .0005). AT-TNF correlated with fasting plasma insulin in Retro only (r = .48, p = .04). AT-TNF activity strongly correlated with cell size in both EPI and Retro (r = .79 and .81, respectively, p < .0001). Because cytokines can be regulated at several levels, AT-TNF activity, protein, and mRNA were measured. AT-TNF protein levels were higher in young rats, suggesting that these animals may secrete an inhibitor that reduces AT-TNF activity. There were no significant differences in AT-TNF mRNA between groups. Since TNF has been shown to affect several key genes in tissue culture, mRNA for lipoprotein lipase, hormone-sensitive lipase, and Glut4 were measured. No differences were found between groups. In summary, AT-TNF activity increased in mature animals in relation to adipose cell size.
此前，高水平的脂肪组织源性肿瘤坏死因子-α（AT-TNF）mRNA和蛋白与肥胖及胰岛素抵抗的遗传模型有关。由于存在内源性肿瘤坏死因子抑制剂，AT-TNF的活性是否也会增加尚不清楚。我们推测，由于脂肪量的积累，老年动物的AT-TNF活性会增加。我们选择研究两种不同年龄的雄性Fischer 344大鼠，3个月大（年轻）和14个月大（成熟），因为脂肪量应该有很大差异，但胰岛素对葡萄糖代谢的作用相似。事实上，成熟大鼠的脂肪量多了1.5倍以上，但通过空腹血浆胰岛素估计的全身胰岛素抵抗与年轻大鼠相似。成熟大鼠附睾（EPI）和腹膜后（Retro）脂肪垫中的AT-TNF活性是年轻大鼠的两倍（p <.0005）。AT-TNF仅与Retro中的空腹血浆胰岛素相关（r =.48，p =.04）。AT-TNF活性与EPI和Retro中的细胞大小均密切相关（分别为r =.79和.81，p <.0001）。由于细胞因子可以在多个水平上受到调节，因此对AT-TNF活性、蛋白和mRNA进行了检测。年轻大鼠的AT-TNF蛋白水平较高，这表明这些动物可能分泌一种降低AT-TNF活性的抑制剂。两组之间的AT-TNF mRNA没有显著差异。由于肿瘤坏死因子已被证明会影响组织培养中的几个关键基因，因此对脂蛋白脂肪酶、激素敏感性脂肪酶和Glut4的mRNA进行了检测。两组之间未发现差异。总之，成熟动物的AT-TNF活性随着脂肪细胞大小的增加而增加。
