Depot-specific regulation of perilipin by rosiglitazone in a diabetic animal model
Depot-specific regulation of perilipin by rosiglitazone in a diabetic animal model
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DOI：
10.1016/j.metabol.2006.12.017
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发表时间：
2007-05-01
影响因子：
9.8
通讯作者：
Cha, Bong Soo
中科院分区：
文献类型：
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作者：
Kim, Hae Jin;Jung, Tae Woo;Cha, Bong Soo
罗格列酮是一种有效的过氧化物酶体增殖物激活受体（PPAR）γ激动剂，可导致脂质蓄积，同时减少游离脂肪酸向循环中的释放。许多研究报道，PPAR-gamma激动剂增加皮下脂肪，但对内脏脂肪量没有影响。脂周蛋白是脂肪细胞内包被脂滴的磷酸化蛋白家族，对脂滴的增大至关重要。最近，一个功能性的PPAR-responsive元件被确定在鼠perilipin基因。我们推测罗格列酮对围脂蛋白的库特异性调节可能与罗格列酮的脂肪再分布和胰岛素增敏作用有关。在2型糖尿病的动物模型Otusuka Long-Evans德岛肥胖大鼠中，罗格列酮治疗6周后，我们测量了肥胖、肝脏和肌肉中甘油三酯含量、胰腺形态以及脂肪组织中围脂蛋白信使RNA和蛋白表达的变化。罗格列酮可增加皮下脂肪，降低肝脏和肌肉的甘油三酯含量，降低血浆游离脂肪酸（安慰剂组为2107 +/- 507 μ mol/L，罗格列酮组为824 +/- 148 μ mol/L; P <0.05），并改善胰岛素抵抗。安慰剂治疗组大鼠的胰岛显示肥大和破坏，而罗格列酮治疗组大鼠的胰岛显示肥大，但胰岛结构保持完整。罗格列酮治疗后，皮下脂肪中周脂信使RNA和蛋白表达增加，但内脏脂肪中无变化。在3 T3-L1细胞中，罗格列酮预处理减少脂解，增加围脂蛋白蛋白。总之，罗格列酮治疗后皮下脂肪中周脂蛋白表达增加可能是脂解减少的介导因素，导致皮下脂肪中的脂质储存、脂肪再分布和胰岛素增敏。(c)2007爱思唯尔公司All rights reserved.
Treatment with rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR) gamma agonist, results in lipid storage coupled with reduced release of free fatty acids into the circulation. Many studies have reported that PPAR-gamma agonists increase subcutaneous adiposity but have no effect on visceral fat mass. Perilipin, a family of phosphoproteins that coat intracellular lipid droplets in adipocytes, is essential for enlargement of lipid droplets. Recently, a functional PPAR-responsive element was identified within the murine perilipin gene. We hypothesized that the depot-specific regulation of perilipin by rosiglitazone may be associated with the fat-redistribution and insulin-sensitizing effects of rosiglitazone. After 6 weeks of rosiglitazone treatment in Otusuka Long-Evans Tokushima Fatty rats, an animal model of type 2 diabetes mellitus, we measured changes in adiposity, triglyceride content in liver and muscle, morphology of the pancreas, and perilipin messenger RNA and protein expression in adipose tissue. Rosiglitazone increased subcutaneous adiposity, decreased triglyceride content of liver and muscle, decreased plasma free fatty acids (2107 +/- 507 mu mol/L in the placebo group vs 824 +/- 148 mu mol/L in the rosiglitazone group; P < .05), and improved insulin resistance. The islets of placebo-treated rats showed hypertrophy and destruction, whereas the islets of rosiglitazone-treated rats showed hypertrophy, but the islet architecture remained intact. Perilipin messenger RNA and protein expression increased in subcutaneous fat, but did not change in visceral fat, after rosiglitazone treatment. In 3T3-L1 cells, rosiglitazone pretreatment decreased lipolysis and increased perilipin protein. In conclusion, increased perilipin expression in subcutaneous fat after rosiglitazone treatment is likely to be a mediator of reduced lipolysis, resulting in lipid storage in subcutaneous fat, fat redistribution, and insulin sensitization. (c) 2007 Elsevier Inc. All rights reserved.