Campbell Jonathan E, Fediuc Sergiu, Hawke Thomas J, Riddell Michael C
School of Kinesiology and Health Science, Faculty of Pure and Applied Science, York University, Toronto, ON, Canada M3J 1P3.
Metabolism. 2009 May;58(5):651-60. doi: 10.1016/j.metabol.2009.01.002.
Glucocorticoids (GCs) have long been thought to be lipolytic in nature. Recently, however, increased exposure to GCs in insulin-sensitive tissues has been associated with lipid accumulation and metabolic complications, regardless of plasma concentrations. Intracellular GC action is determined by both 11-beta hydroxysteroid dehydrogenase type 1 (11betaHSD1) and the GC receptor (GR). We hypothesized that exercise training would increase 11betaHSD1 and GR protein in adipose tissue, resulting in increased lipolysis. To test the effects of exercise on adipose tissue GR and 11betaHSD1 protein, 2 sets of hamsters were trained for 6 weeks: young, diet-induced obese animals and older, overweight animals. Young (6 week old) hamsters, fructose-fed to induce an obese phenotype, and older (6 month old) hamsters were randomly divided into exercising and sedentary groups. Exercise training decreased adipose tissue mass in both fructose-fed and older hamsters. In addition, exercise training increased 11betaHSD1 (31.5% +/- 15% and 20.0% +/- 7%, fructose-fed and older, respectively) and GR (45.6% +/- 14% and 61.1% +/- 27%, fructose-fed and older, respectively) protein expression in the perirenal adipose depot and increased 11betaHSD1 (16.7% +/- 7%, P = .09) and GR (47.4% +/- 19%, P < .05) in the subcutaneous adipose depot of the older hamsters. To determine the metabolic effect of increased GC exposure in adipocytes, 3T3-L1 adipocytes were treated with corticosterone for 24 hours; and measures of lipolytic rates were conducted. Low concentrations of GCs (0.01-0.1 micromol/L) increased GR (44.1% +/- 18%, P < .05) and 11betaHSD1 (95.3% +/- 24%) protein expression, as well as lipolytic rates (34.6% +/- 6%) as measured by glycerol release. The increased lipolysis was blocked by RU486, a GR antagonist, suggesting that the elevated lipolysis was a direct result of GC action. These results suggest that exercise training amplifies the activity of GCs in adipose tissue of overweight animals through alterations in 11betaHSD1 and GR despite differences in age and amounts of adiposity. In vitro, GCs are capable of increasing lipolysis, but depend upon the presence of GR. We propose that GCs play a significant role in changing the phenotype of adipose tissue during exercise training, resulting in decreased fat mass.
长期以来，人们一直认为糖皮质激素（GCs）具有脂解作用。然而，最近的研究发现，在胰岛素敏感组织中，无论血浆浓度如何，GCs暴露增加都与脂质积累和代谢并发症有关。细胞内GC的作用由11-β羟类固醇脱氢酶1型（11βHSD1）和GC受体（GR）共同决定。我们推测，运动训练会增加脂肪组织中11βHSD1和GR蛋白的表达，从而增强脂解作用。为了测试运动对脂肪组织GR和11βHSD1蛋白的影响，我们将两组仓鼠进行了为期6周的训练：年轻的、饮食诱导肥胖的动物和年长的、超重的动物。将年轻（6周龄）的仓鼠喂食果糖以诱导肥胖表型，年长（6月龄）的仓鼠随机分为运动组和 sedentary组。运动训练使喂食果糖的仓鼠和年长仓鼠的脂肪组织质量均有所下降。此外，运动训练使肾周脂肪库中11βHSD1（分别为31.5%±15%和20.0%±7%，喂食果糖组和年长组）和GR（分别为45.6%±14%和61.1%±27%，喂食果糖组和年长组）的蛋白表达增加，并使年长仓鼠皮下脂肪库中11βHSD1（16.7%±7%，P = 0.09）和GR（47.4%±19%，P < 0.05）增加。为了确定GC暴露增加对脂肪细胞代谢的影响，我们用皮质酮处理3T3-L1脂肪细胞24小时，并测量脂解速率。低浓度的GCs（0.01-0.1 μmol/L）增加了GR（44.1%±18%，P < 0.05）和11βHSD1（95.3%±24%）的蛋白表达，以及甘油释放所测量的脂解速率（34.6%±6%）。GR拮抗剂RU486阻断了脂解作用的增加，这表明脂解作用的增强是GC作用的直接结果。这些结果表明，尽管年龄和肥胖程度不同，但运动训练通过改变11βHSD1和GR来增强超重动物脂肪组织中GCs的活性。在体外，GCs能够增加脂解作用，但依赖于GR的存在。我们认为，GCs在运动训练期间改变脂肪组织表型方面发挥着重要作用，从而导致脂肪量减少。
