Zhang Xianrui, Li Wenguo, Zhou Tiantian, Liu Meng, Wu Qingyu, Dong Ningzheng
Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou 215123, China.
MOH Key Laboratory of Thrombosis and Hemostasis, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Biology (Basel). 2022 Jul 23;11(8):1101. doi: 10.3390/biology11081101.
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 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.
心房利钠肽（ANP）是体液平衡和心血管生物学中的关键调节因子。除了其在增强利钠作用和血管舒张方面的作用外，ANP还能增加脂肪组织中的脂肪分解和产热。Corin是一种负责激活ANP的蛋白酶。Corin是否在调节脂肪组织功能中发挥作用尚不清楚。在此，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，WAT和棕色脂肪组织（BAT）中棕色脂肪细胞标志物解偶联蛋白1（Ucp1）的水平降低，并且Corin基因敲除小鼠BAT中的产热基因表达受到抑制。在正常室温下，Corin基因敲除小鼠和野生型小鼠的代谢率相似。在4℃冷暴露后，Corin基因敲除小鼠表现出产热反应受损并出现体温过低。在Corin基因敲除小鼠的BAT中，p38丝裂原活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α和Ucp1的信号通路受损。在细胞培养中，ANP处理增加了Corin基因敲除小鼠BAT来源的脂肪细胞中的表达。这些数据表明，Corin介导的ANP激活是调节小鼠冷暴露时脂肪组织功能和体温的重要激素机制。
