Age-related onset of obesity corresponds with metabolic dysregulation and altered microglia morphology in mice deficient for Ifitm proteins.
Age-related onset of obesity corresponds with metabolic dysregulation and altered microglia morphology in mice deficient for Ifitm proteins.
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DOI：
10.1371/journal.pone.0123218
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Weis JH
中科院分区：
文献类型：
--
作者：
Wee YS;Weis JJ;Gahring LC;Rogers SW;Weis JH
IfitmDel 小鼠通过 LoxP 缺失而缺乏所有五个 Ifitm 基因。这种动物繁殖正常，没有明显的发育缺陷。与野生型对照相比，IfitmDel 动物在大约三个月龄开始且在正常喂养条件下表现出稳定且显着增加的体重增加。体重增加与脂肪量增加相对应，在耐受性测试中，它们对胰岛素反应低下，但对葡萄糖反应正常。年轻（4 个月）和年长（12 个月）IfitmDel 小鼠的血清瘦素水平均升高，表明瘦素/瘦素受体信号传导存在缺陷。与 WT 相比，对 IfitmDel 动物下丘脑基因表达谱的分析表明，Pomc 和 Npy 神经肽表达比例发生了变化，这可能会损害 IfitmDel 动物的饱足反应，导致进食行为增加。 IfitmDel 小鼠下丘脑的促炎细胞因子表达也升高，IL-10 减少。使用免疫组织化学对下丘脑进行的解剖分析表明，IfitmDel 动物中的小胶质细胞表现出异常形态，并对 Poly:IC 攻击做出异常反应。这些异常使 IfitmDel 小鼠的表型超出了对病毒攻击的异常反应，包括代谢表型和体重增加。此外，IfitmDel 小鼠的这种新表型可能与下丘脑中异常的神经肽产生、炎症状态和小胶质细胞状态有关。
The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This animal breeds normally with no obvious defect in development. The IfitmDel animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months of age and under normal feeding conditions. The increased weight corresponds with elevated fat mass, and in tolerance tests they are hyporesponsive to insulin but respond normally to glucose. Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels of serum leptin suggesting a defect in leptin/leptin receptor signaling. Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. Also elevated in hypothalamus of IfitmDel mice were pro-inflammatory cytokine expression and reduced IL-10. Anatomical analysis of the hypothalamus using immunohistochemistry revealed that microglia exhibit an abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC challenge. These abnormalities extend the phenotype of the IfitmDel mouse beyond abnormal responses to viral challenge to include a metabolic phenotype and weight gain. Further, this novel phenotype for the IfitmDel mouse could be related to abnormal neuropeptide production, inflammatory status and microglia status in the hypothalamus.
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影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
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影响因子：
30.3
作者：
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影响因子：
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影响因子：
3.1
作者：
Brown, Charles R.;Lai, Annie Y. -C.;Mitchell, William J.
通讯作者：
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影响因子：
2
作者：
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通讯作者：
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