Metabolic and cellular plasticity in white adipose tissue I:: effects of β3-adrenergic receptor activation
Metabolic and cellular plasticity in white adipose tissue I:: effects of β3-adrenergic receptor activation
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DOI：
10.1152/ajpendo.00009.2005
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发表时间：
2005-10-01
影响因子：
5.1
通讯作者：
Lu, YY
中科院分区：
文献类型：
--
作者：
Granneman, JG;Li, PP;Lu, YY
β(3)-肾上腺素能受体（Adrb3）的选择性激动剂在啮齿类动物模型中表现出有效的抗糖尿病特性，但其机制尚不清楚。慢性Adrb3激活的一个显著特征是白色脂肪组织（WAT）的显著重塑，包括线粒体生物发生和代谢率升高。为了深入了解WAT重塑的潜在机制，我们使用组织学、生理学和全局基因谱方法分析了Adrb3激动剂CL-316,243 （CL）诱导WAT重塑的时间过程。结果表明，持续的CL治疗诱导了短暂的促炎反应，随后是基质细胞和多室脂肪细胞之间的细胞增殖。CL处理强烈分裂了成熟脂肪细胞的中央脂质储存液滴，并诱导了这些细胞内的线粒体生物发生。线粒体生物发生与脂肪酸氧化和线粒体电子传递活性相关的基因上调有关。WAT分解代谢活性的升高与过氧化物酶体增殖物激活受体α及其靶基因的上调有时间相关性，表明该转录因子参与协调提高WAT分解代谢活性的基因程序。
Selective agonists of beta(3)-adrenergic receptors (Adrb3) exhibit potent anti-diabetes properties in rodent models when given chronically, yet the mechanisms involved are poorly understood. A salient feature of chronic Adrb3 activation is pronounced remodeling of white adipose tissue (WAT), which includes mitochondrial biogenesis and elevation of metabolic rate. To gain insights into potential mechanisms underlying WAT remodeling, the time course of remodeling induced by the Adrb3 agonist CL-316,243 (CL) was analyzed using histological, physiological, and global gene profiling approaches. The results indicate that continuous CL treatment induced a transient proinflammatory response that was followed by cellular proliferation among stromal cells and multilocular adipoctyes. CL treatment strongly fragmented the central lipid storage droplet of mature adipocytes and induced mitochondrial biogenesis within these cells. Mitochondrial biogenesis was correlated with the upregulation of genes involved in fatty acid oxidation and mitochondrial electron transport activity. The elevated catabolic activity of WAT was temporally correlated with upregulation of peroxisome proliferator-activated receptor-alpha and its target genes, suggesting involvement of this transcription factor in coordinating the gene program that elevates WAT catabolic activity.