Metabolic and cellular plasticity in white adipose tissue II:: role of peroxisome proliferator-activated receptor-α
Metabolic and cellular plasticity in white adipose tissue II:: role of peroxisome proliferator-activated receptor-α
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DOI：
10.1152/ajpendo.00010.2005
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发表时间：
2005-10-01
影响因子：
5.1
通讯作者：
Granneman, JG
中科院分区：
文献类型：
--
作者：
Li, PP;Zhu, ZX;Granneman, JG
脂肪细胞β-肾上腺素能受体的慢性激活诱导白色脂肪组织（WAT）的重塑，包括短暂的炎症反应，随后是线粒体生物发生、脂肪酸氧化基因的诱导和组织氧化代谢的升高。β 3肾上腺素能受体激动剂CL-316，243（CL）诱导的重塑过程中WAT的基因分析实验表明，CL上调的过氧化物酶体增殖物激活受体α（Ppara）可能是该过程的重要转录调节因子。在野生型小鼠和缺乏Ppara的小鼠中CL诱导的重塑的组织学、生理学和分子分析表明，Ppara对于诱导脂肪细胞线粒体生物合成和上调参与脂肪酸氧化的基因是重要的。此外，Ppara缺陷小鼠在CL治疗期间表现出持续的WAT炎症，表明Ppara的上调限制了慢性脂解激活期间的促炎信号传导。总之，这些数据支持WAT重塑是对过度脂肪酸动员的适应性反应的假设，其中Ppara及其下游靶点升高脂肪酸催化剂并抑制促炎信号传导。
Chronic activation of adipocyte beta-adrenergic receptors induces remodeling of white adipose tissue (WAT) that includes a transient inflammatory response followed by mitochondrial biogenesis, induction of fatty acid oxidation genes, and elevation of tissue oxidative metabolism. Gene profiling experiments of WAT during remodeling induced by the beta(3)-adrenergic receptor agonist CL-316,243 (CL) suggested that peroxisome proliferator-activated receptor-alpha (Ppara), which is upregulated by CL, might be an important transcriptional regulator of that process. Histological, physiological, and molecular analysis of CL-induced remodeling in wild-type mice and mice lacking Ppara demonstrated that Ppara was important for inducing adipocyte mitochondrial biogenesis and upregulating genes involved in fatty acid oxidation. Furthermore, Ppara-deficient mice exhibited sustained WAT inflammation during CL treatment, indicating that upregulation of Ppara limits proinflammatory signaling during chronic lipolytic activation. Together, these data support the hypothesis that WAT remodeling is an adaptive response to excessive fatty acid mobilization whereby Ppara and its downstream targets elevate fatty acid catabolism and suppress proinflammatory signaling.