Loss of miR-146b-3p Inhibits Perivascular Adipocyte Browning with Cold Exposure During Aging
Loss of miR-146b-3p Inhibits Perivascular Adipocyte Browning with Cold Exposure During Aging
复制标题
miR-146b-3p 的缺失抑制衰老过程中血管周围脂肪细胞因冷暴露而褐变
DOI：
10.1007/s10557-018-6814-x
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发表时间：
2018-10-01
影响因子：
3.4
通讯作者：
Gao, Ping-Jin
中科院分区：
文献类型：
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作者：
Pan, Xiao-Xi;Cao, Jiu-Mei;Gao, Ping-Jin
目的血管周围脂肪组织（PVAT）的病理变化与年龄相关血管疾病的风险增加直接相关。 MicroRNA 调节脂肪细胞的生物学功能，包括脂肪形成分化和白色脂肪细胞褐变。本研究旨在确定miR-146b-3p是否参与衰老过程中血管周围脂肪细胞褐变的调节。方法采用寒冷诱导的动物模型研究衰老对血管周围脂肪细胞褐变的影响。我们还检测了冷刺激后年轻或年老小鼠PVAT中miR-146b-3p的表达。我们通过给予miRNA模拟物或抑制剂进一步研究了miR-146b-3p在体外和体内调节血管周围脂肪细胞褐变的作用。结果老年小鼠在冷刺激后表现出血管周围脂肪细胞褐变减少以及PVAT中miR-146b-3p表达下调。油红O染色和qPCR表明，衰老扰乱了前脂肪细胞向棕色脂肪细胞的分化，并且在分化过程中miR-146b-3p的表达逐渐增加。 miR-146b-3p 抑制剂阻断年轻前脂肪细胞中的棕色脂肪细胞分化，而 miR-146b-3p 模拟物则挽救老前脂肪细胞的分化。最后，miR-146b-3p 敲低冷刺激后年轻小鼠血管周围脂肪细胞褐变的抑制。结论衰老抑制血管周围脂肪细胞褐变，miR-146b-3p 的缺失是这一过程的潜在调节因子。
PurposePathological changes of the perivascular adipose tissue (PVAT) are directly associated with increased risk of age-related vascular diseases. MicroRNAs regulate adipocyte biological functions including adipogenic differentiation and white adipocyte browning. The present study aims to determine whether miR-146b-3p is involved in the regulation of perivascular adipocyte browning during aging.MethodsWe utilized a cold-induced animal model to investigate the effect of aging on perivascular adipocyte browning. We also detected the miR-146b-3p expression in the PVAT of young or old mice after cold stimulus. We further investigated the role of miR-146b-3p in regulating perivascular adipocyte browning in vitro and in vivo via administrating miRNA mimics or inhibitors.ResultsOld mice showed decrease of perivascular adipocyte browning and downregulation of miR-146b-3p expression in the PVAT after cold stimulus. Oil red O staining and qPCR indicated that aging perturbed preadipocyte to brown adipocyte differentiation, and expression of miR-146b-3p gradually increased during differentiation. MiR-146b-3p inhibitors blocked brown adipocyte differentiation in young preadipocytes, whereas miR-146b-3p mimics rescued the differentiation of the old preadipocytes. Finally, miR-146b-3p knocks down inhibited perivascular adipocyte browning in young mice after cold stimulus.ConclusionAging inhibits perivascular adipocyte browning, and loss of miR-146b-3p is a potential regulator for this process.