Irisin exerts dual effects on browning and adipogenesis of human white adipocytes
Irisin exerts dual effects on browning and adipogenesis of human white adipocytes
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DOI：
10.1152/ajpendo.00094.2016
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发表时间：
2016-08-01
影响因子：
5.1
通讯作者：
Yang, Li-Jun
中科院分区：
文献类型：
--
作者：
Zhang, Yuan;Xie, Chao;Yang, Li-Jun
为了更好地理解鸢尾素在人体中的作用，我们检查了鸢尾素在人原代脂肪细胞和新鲜人皮下白色脂肪组织（scWAT）中的作用。使用来自28名女性供体的新鲜scWAT的人原代脂肪细胞来检测鸢尾素对布朗宁和线粒体呼吸的影响，并且使用前脂肪细胞来检测鸢尾素对脂肪生成和骨生成的影响。培养的scWAT片段和肾周棕色脂肪用于研究介导鸢尾素的布朗宁效应的信号转导途径，通过Western印迹检测磷酸化形式的p38、ERK和STAT 3以及解偶联蛋白1（UCP 1）。scWAT中对鸢尾素的个体反应与棕色/米色基因的基础表达水平相关。鸢尾素上调培养的原代成熟脂肪细胞和新鲜脂肪组织中褐化相关基因和UCP1蛋白的表达。它还通过提高细胞能量代谢（OCR和ECAR）显著增加了5 nmol/l的产热作用。用鸢尾素处理人scWAT通过激活ERK和p38 MAPK信号传导增加UCP1表达。阻断任一途径与特定的抑制剂废除irisin诱导的UCP1上调。然而，我们的研究结果表明，UCP1在人肾周脂肪组织是不敏感的鸢尾素。棕色/米色和FNDC5基因的基础水平与scWAT对鸢尾素的布朗宁反应正相关。此外，鸢尾素显着抑制成脂分化，但促进成骨分化。我们的结论是，鸢尾素促进"布朗宁"的成熟白色脂肪细胞，通过增加细胞产热，而它抑制脂肪生成和促进成骨过程中的谱系特异性分化。我们的研究结果为进一步探索鸢尾素在肥胖和运动相关骨形成中的治疗用途提供了理论基础。
To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes "browning" of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exerciseassociated bone formation.