Corin Deficiency Alters Adipose Tissue Phenotype and Impairs Thermogenesis in Mice.
Corin Deficiency Alters Adipose Tissue Phenotype and Impairs Thermogenesis in Mice.
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Corin 缺乏会改变小鼠的脂肪组织表型并损害生热作用
DOI：
10.3390/biology11081101
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发表时间：
2022-07-23
期刊：
影响因子：
4.2
通讯作者：
Dong, Ningzheng
中科院分区：
文献类型：
--
作者：
Zhang, Xianrui;Li, Wenguo;Zhou, Tiantian;Liu, Meng;Wu, Qingyu;Dong, Ningzheng
体温调节对于所有吸热动物都具有根本意义。Corin是一种激活心房利钠肽（ANP）的蛋白酶，心房利钠肽是一种对心血管稳态和脂肪组织功能至关重要的心脏激素。在这项研究中，我们报告说，在小鼠中，corin缺乏增加的重量和细胞大小的白色脂肪组织，减少产热基因在棕色脂肪组织的档案，并削弱产热反应后，冷暴露，导致体温过低。在corin缺陷小鼠的棕色脂肪组织中，ANP介导的p38丝裂原活化蛋白激酶和解偶联蛋白1信号传导机制受到损害。这些发现表明corin在调节小鼠冷暴露后脂肪组织功能和产热方面的重要作用。心房利钠肽（ANP）是体液平衡和心血管生物学的关键调节因子。除了其在增强尿钠排泄和血管舒张中的作用外，ANP还增加脂肪组织中的脂解和产热。Corin是一种负责ANP激活的蛋白酶。它仍然是未知的，如果corin有调节脂肪组织功能的作用。在这里，我们研究了corin基因敲除（KO）小鼠的脂肪组织形态和功能。我们观察到白色脂肪组织（WAT）的重量和细胞大小增加，解偶联蛋白1（Ucp 1）水平降低，WAT和棕色脂肪组织（BAT）中的棕色脂肪细胞标记物，并抑制corin KO小鼠BAT中的产热基因表达。在正常室温下，corin KO和野生型小鼠的代谢率相似。在4 °C冷暴露后，corin KO小鼠表现出产热反应受损并出现体温过低。在来自corin KO小鼠的BAT中，p38丝裂原活化蛋白激酶、过氧化物酶体增殖物活化受体c共激活因子1a和Ucp1的信号通路受损。在细胞培养中，ANP处理增加了corin KO小鼠BAT衍生脂肪细胞中Ucp1的表达。这些数据表明，corin介导的心钠素激活是一个重要的激素机制，在调节脂肪组织功能和体温后，冷暴露在小鼠。
Thermoregulation is of fundamental significance for all endothermic animals. Corin is a protease that activates atrial natriuretic peptide (ANP), a cardiac hormone critical in cardiovascular homeostasis and adipose tissue function. In this study, we report that in mice, corin deficiency increased the weight and cell size in white adipose tissue, decreased thermogenic gene profiles in brown adipose tissue, and impaired thermogenic responses upon cold exposure, leading to hypothermia. In brown adipose tissue from corin-deficient mice, the ANP-mediated p38 mitogen-activated protein kinase and uncoupling protein 1 signaling mechanism is compromised. These findings indicate a crucial role of corin in modulating adipose tissue function and thermogenesis upon cold exposure in mice. Atrial natriuretic peptide (ANP) is a key regulator in body fluid balance and cardiovascular biology. In addition to its role in enhancing natriuresis and vasodilation, ANP increases lipolysis and thermogenesis in adipose tissue. Corin is a protease responsible for ANP activation. It remains unknown if corin has a role in regulating adipose tissue function. Here, we examined adipose tissue morphology and function in corin knockout (KO) mice. We observed increased weights and cell sizes in white adipose tissue (WAT), decreased levels of uncoupling protein 1 (Ucp1), a brown adipocyte marker in WAT and brown adipose tissue (BAT), and suppressed thermogenic gene expression in BAT from corin KO mice. At regular room temperature, corin KO and wild-type mice had similar metabolic rates. Upon cold exposure at 4 °C, corin KO mice exhibited impaired thermogenic responses and developed hypothermia. In BAT from corin KO mice, the signaling pathway of p38 mitogen-activated protein kinase, peroxisome proliferator-activated receptor c coactivator 1a, and Ucp1 was impaired. In cell culture, ANP treatment increased Ucp1 expression in BAT-derived adipocytes from corin KO mice. These data indicate that corin mediated-ANP activation is an important hormonal mechanism in regulating adipose tissue function and body temperature upon cold exposure in mice.
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Corin 和心钠素在人肾段表达的定位
DOI：
10.1042/cs20160398
发表时间：
2016-09-01
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Dong L;Wang H;Dong N;Zhang C;Xue B;Wu Q
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影响因子：
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DOI：
10.1073/pnas.0407234102
发表时间：
2005-01-18
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
9.3
作者：
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通讯作者：
Burnett, John C., Jr.
DOI：
10.1152/ajpendo.00023.2015
发表时间：
2015-06-15
影响因子：
5.1
作者：
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通讯作者：
Nedergaard, Jan