Disordered metabolism in mice lacking irisin.

Disordered metabolism in mice lacking irisin.
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缺乏鸢尾素的小鼠新陈代谢紊乱

DOI:
10.1038/s41598-020-74588-7
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发表时间:
2020-10-15
期刊:
影响因子:
4.6
通讯作者:
Xu L
Xu L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Luo Y;Qiao X;Ma Y;Deng H;Xu CC;Xu L

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鸢尾素是含纤连蛋白III型结构域蛋白(Fndc5)的产物,参与脂肪因子分泌的调节以及成骨细胞和破骨细胞的分化。在本研究中,我们旨在确定鸢尾素缺失是否会影响糖脂代谢和骨代谢。我们敲除Fndc5基因以培育出缺乏鸢尾素的小鼠。值得注意的是,鸢尾素缺失与“米色化反应”不佳有关,表现为腹膜内白色脂肪细胞体积增大,肩胛间组织棕色脂肪中的棕色脂肪细胞数量减少。缺乏鸢尾素的小鼠出现高血脂和胰岛素抵抗,高密度脂蛋白胆固醇水平降低,低密度脂蛋白胆固醇水平升高,胰岛素敏感性下降。鸢尾素缺失与小鼠骨强度和骨量降低相关。破骨细胞数量增加以及核因子κB受体活化因子配体(RANKL)表达升高表明,缺乏鸢尾素的小鼠骨吸收增加。缺乏鸢尾素的小鼠体内白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平也有所上升。研究结果显示,鸢尾素缺失与“米色化反应”减弱、糖脂代谢紊乱以及骨量减少且骨吸收增加有关。需要进一步研究来证实这些初步观察结果,并探究鸢尾素对糖脂代谢和骨代谢产生影响的潜在机制。
Irisin is a product of fibronectin type III domain-containing protein (Fndc5) and is involved in the regulation of adipokine secretion and the differentiation of osteoblasts and osteoclasts. In this study, we aimed to determine whether irisin lacking affects glucose/lipid and bone metabolism. We knocked out theFndc5gene to generate irisin-lacking mice. Remarkable, irisin lacking was related to poor ‘browning response’, with a bigger size of the intraperitoneal white adipose cell and decreased a number of brown adipose cells in brown adipose of interscapular tissue. The irisin lacking mice had hyperlipidemia and insulin resistance, reduced HDL-cholesterol level, increased LDL-cholesterol level, and decreased insulin sensitivity. The lacking of irisin was associated with reduced bone strength and bone mass in mice. The increased number of osteoclasts and higher expression of RANKL indicated increased bone resorption in irisin lacking mice. The level of IL-6 and TNF-α also increased in irisin lacking mice. The results showed that irisin lacking was related to decreased ‘browning response’, glucose/lipid metabolic derangement, and reduced bone mass with increased bone resorption. Further studies are needed to confirm these initial observations and explore the mechanisms underlying the effects of irisin on glucose/lipid and bone metabolism.
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发表时间: 2015-03
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