Asayama K, Nakane T, Dobashi K, Kodera K, Hayashibe H, Uchida N, Nakazawa S
Department of Pediatrics, Yamanashi Medical University, 1110 Shimokato, Tamahocho, Nakakomagun, Yamanashi 409-3898, Japan.
Free Radic Res. 2001 Apr;34(4):337-47. doi: 10.1080/10715760100300291.
To determine the effect of obesity on expression of cellular- (C-) and extracellular (EC-) glutathione peroxidase (GPX) in serum, kidney and adipose tissue, we measured GPX in serum, kidneys and adipose tissue of the obese Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat and its lean counterpart (LETO). We also investigated the effect of troglitazone. Five each of OLETF and LETO rats were fed diet with or without 0.2% troglitazone for 10 days. Final body weight, kidney weight, blood glucose and serum tumor necrosis factor-alpha (TNF-alpha) level were higher in OLETF rats than in LETO rats. Serum and kidney GPX activities were higher, but adipose tissue GPX activity was lower, in OLETF rats than in LETO rats. Troglitazone treatment decreased adipose tissue GPX activity and abolished overproduction of TNF-alpha in OLETF rats. Immunoblot analysis, for the first time, revealed that both obesity and troglitazone suppressed the protein signals for C-GPX and EC-GPX in adipose tissue. Serum protein carbonyl groups were increased in OLETF rats and troglitazone completely blocked this increase. Increased serum GPX activity in obese rat was due to the increased secretion of EC-GPX from the kidney. Troglitazone protected against the enhanced oxidative stress induced by obesity independently of the serum GPX concentration.
为了确定肥胖对血清、肾脏和脂肪组织中细胞内（C-）和细胞外（EC-）谷胱甘肽过氧化物酶（GPX）表达的影响，我们测量了肥胖的大冢-长-艾维斯-德岛肥胖（OLETF）大鼠及其瘦型对照（LETO）大鼠的血清、肾脏和脂肪组织中的GPX。我们还研究了曲格列酮的作用。将五只OLETF大鼠和五只LETO大鼠分别喂食含或不含0.2%曲格列酮的饲料10天。OLETF大鼠的终末体重、肾脏重量、血糖和血清肿瘤坏死因子-α（TNF-α）水平均高于LETO大鼠。与LETO大鼠相比，OLETF大鼠的血清和肾脏GPX活性较高，但脂肪组织GPX活性较低。曲格列酮治疗降低了OLETF大鼠脂肪组织的GPX活性，并消除了TNF-α的过量产生。免疫印迹分析首次显示，肥胖和曲格列酮均抑制了脂肪组织中C-GPX和EC-GPX的蛋白信号。OLETF大鼠血清蛋白羰基增加，曲格列酮完全阻止了这种增加。肥胖大鼠血清GPX活性增加是由于肾脏EC-GPX分泌增加。曲格列酮独立于血清GPX浓度，对肥胖诱导的氧化应激增强具有保护作用。
