Activation of peroxisome proliferator-activated receptor-α enhances fatty acid oxidation in human adipocytes
Activation of peroxisome proliferator-activated receptor-α enhances fatty acid oxidation in human adipocytes
复制标题
DOI：
10.1016/j.bbrc.2011.03.106
复制
发表时间：
2011-04-22
影响因子：
3.1
通讯作者：
Kawada, Teruo
中科院分区：
文献类型：
--
作者：
Lee, Joo-Young;Hashizaki, Hikari;Kawada, Teruo
过氧化物酶体增殖激活受体α (PPAR α)是维持全身能量平衡的关键调节因子。然而，PPAR α在脂肪细胞中的生理功能尚不清楚。我们使用人类多能脂肪组织来源的干细胞作为人类脂肪细胞模型来检测PPAR α的功能。GW7647（一种有效的PPAR α激动剂）激活PPAR α，增加了脂肪细胞分化标记基因（如PPAR γ、脂肪细胞特异性脂肪酸结合蛋白和脂蛋白脂肪酶）的mRNA表达水平，并增加了GPDH活性和胰岛素依赖性葡萄糖摄取水平。研究结果表明，PPAR α激活刺激脂肪细胞分化。然而，脂质积累没有改变，这通常是在PPAR γ激活时观察到的。另一方面，GW7647处理激活PPAR α诱导脂肪酸氧化相关基因如CPT-1B和AOX的mRNA以PPAR α依赖的方式表达。此外，PPAR α激活增加了脂肪酸氧化产物CO2和酸溶性代谢物的产生，并增加了人体脂肪细胞的耗氧量。数据表明，PPAR α的激活可以刺激人脂肪细胞的脂肪细胞分化和脂肪酸氧化，提示PPAR α激动剂可以改善胰岛素抵抗，而不会在脂肪细胞中积累脂质。PPAR α激活的预期效果对于治疗伴有肥胖的糖尿病非常有价值，因为PPAR γ激动剂通常用作降糖药，除了改善胰岛素抵抗外，还会诱导脂肪细胞过度的脂质积累。(C) 2011爱思唯尔公司版权所有。
Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR alpha in adipocytes have been unclarified. We examined the functions of PPAR alpha using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR alpha by GW7647, a potent PPAR alpha agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR gamma, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR alpha activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR gamma is activated. On the other hand, PPAR alpha activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR alpha-dependent manner. Moreover, PPAR alpha activation increased the production of CO2 and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR alpha stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR alpha agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPAR alpha activation are very valuable for managing diabetic conditions accompanied by obesity, because PPAR gamma agonists, usually used as antidiabetic drugs, induce excessive lipid accumulation in adipocytes in addition to improvement of insulin resistance. (C) 2011 Elsevier Inc. All rights reserved.