Norepinephrine and rosiglitazone synergistically induce Elov13 expression in brown adipocytes
Norepinephrine and rosiglitazone synergistically induce Elov13 expression in brown adipocytes
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DOI：
10.1152/ajpendo.00213.2007
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发表时间：
2007-11-01
影响因子：
5.1
通讯作者：
Jacobsson, Anders
中科院分区：
文献类型：
--
作者：
Jorgensen, Johanna A.;Zadravec, Damir;Jacobsson, Anders
Elovl3基因在小鼠肝脏、皮肤和棕色脂肪组织(BAT)中表达，推测编码一种蛋白质，参与C20-C24范围内饱和脂肪酸和单不饱和脂肪酸的延伸。在BAT中，Elovl3在冷暴露下的组织激活过程中显著上调，功能数据表明，在组织募集的早期阶段，ELOVL3是棕色脂肪细胞中脂质积累的关键酶。BAT的激活受交感神经活动和去甲肾上腺素释放的控制。通过棕色脂肪细胞的原代培养，我们证明了诱导的Elovl3基因的表达是由去甲肾上腺素和过氧化体增殖物激活受体(PPAR)γ配体罗格列酮协同调节的。此外，罗格列酮诱导Elov13表达的效力分别比PPARα和PPAR增量配体WY-14643和L-165041高几个数量级。去甲肾上腺素和罗格列酮通过诱导转录和增加mRNA的稳定性来最大限度地提高mRNA水平，整个过程需要新的蛋白质合成。我们得出的结论是，尽管去甲肾上腺素和PPAR-γ在棕色脂肪细胞的激活和分化中具有不同的作用，但它们通过协同刺激Elovl3的表达来扩大细胞内的脂库。
The Elovl3 gene, which putatively encodes for a protein involved in the elongation of saturated and monounsaturated fatty acids in the C20 - C24 range, is expressed in murine liver, skin, and brown adipose tissue ( BAT). In BAT, Elovl3 is dramatically upregulated during tissue activation in response to cold exposure, and functional data imply that ELOVL3 is a critical enzyme for lipid accumulation in brown adipocytes during the early phase of tissue recruitment. The activation of BAT is controlled by sympathetic nerve activity and norepinephrine release. By using primary cultures of brown adipocytes, we show here that the induced Elovl3 gene expression is synergistically regulated by norepinephrine and the peroxisome proliferator-activated receptor ( PPAR) gamma ligand rosiglitazone. In addition, the potency of rosiglitazone to induce Elovl3 expression was several orders of magnitude higher than for the PPAR alpha and PPAR delta ligands WY-14643 and L-165041, respectively. The maximal increase in mRNA level by norepinephrine and rosiglitazone is achieved by induced transcription as well as increased mRNA stability, and the whole process requires novel protein synthesis. We conclude that norepinehrine and PPAR gamma, despite having different roles in brown adipocyte activation and differentiation, cooperate in expanding the intracellular lipid pool by synergistically stimulating Elovl3 expression.