miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARγ expression

miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARγ expression
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DOI:
10.1016/j.bbrc.2010.01.012
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发表时间:
2010-02-12
影响因子:
3.1
通讯作者:
Kim, Jae Bum
Kim, Jae Bum
中科院分区:
生物学4区
文献类型:
--
作者:
Kim, Sang Yun;Kim, A. Young;Kim, Jae Bum

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microRNAs (miRNAs)是调节基因表达、细胞生长和分化的非编码小rna,虽然有几种miRNAs与细胞生长和分化有关,但对它们在脂肪细胞分化中的作用知之甚少。在本研究中,我们发现miR-27a通过结合PPAR γ 3'-UTR参与脂肪细胞分化,其序列基序在哺乳动物中高度保守。在脂肪形成过程中,miR-27a的表达水平与PPAR γ和脂联素等脂肪生成标记基因的表达水平呈负相关。在白色脂肪组织中,miR-27a在基质血管细胞中比在成熟脂肪细胞中表达更丰富。有趣的是,3T3-L1前脂肪细胞中miR-27a的异位表达通过降低PPAR γ的表达来抑制脂肪细胞分化。肥胖小鼠成熟脂肪细胞中miR-27a水平明显低于瘦小鼠。这些结果表明,miR-27a通过靶向PPAR γ抑制脂肪细胞分化,因此miR-27a的调控可能与肥胖中脂肪组织失调有关(C) 2010 Elsevier Inc .版权所有。
microRNAs (miRNAs) are non-coding small RNAs regulating gene expression, cell growth, and differentiation Although several miRNAs have been implicated in cell growth and differentiation, it is barely understood their roles in adipocyte differentiation. In the present Study, we reveal that miR-27a is involved in adipocyte differentiation by binding to the PPAR gamma 3'-UTR whose sequence motifs are highly conserved in mammals. During adipogenesis, the expression level of miR-27a was inversely correlated with that of adipogenic marker genes such as PPAR gamma and adiponectin In white adipose tissue, miR-27a was more abundantly expressed in stromal vascular cell fraction than in mature adipocyte fraction Ectopic expression of miR-27a in 3T3-L1 pre-adipocytes repressed adipocyte differentiation by reducing PPAR gamma expression Interestingly, the level of miR-27a in mature adipocyte fraction of obese mice was down-regulated than that of lean mice Together. these results suggest that miR-27a would suppress adipocyte differentiation through targeting PPAR gamma and thereby clown-regulation of miR-27a might be associated with adipose tissue dysregulation in obesity (C) 2010 Elsevier Inc All rights reserved.