Wu Qingyu, Li Shuo, Zhang Xianrui, Dong Ningzheng
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou 215123, China.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Biomedicines. 2023 Jun 23;11(7):1794. doi: 10.3390/biomedicines11071794.
Adipose tissue is a crucial organ in energy metabolism and thermoregulation. Adipose tissue phenotype is controlled by various signaling mechanisms under pathophysiological conditions. Type II transmembrane serine proteases (TTSPs) are a group of trypsin-like enzymes anchoring on the cell surface. These proteases act in diverse tissues to regulate physiological processes, such as food digestion, salt-water balance, iron metabolism, epithelial integrity, and auditory nerve development. More recently, several members of the TTSP family, namely, hepsin, matriptase-2, and corin, have been shown to play a role in regulating lipid metabolism, adipose tissue phenotype, and thermogenesis, via direct growth factor activation or indirect hormonal mechanisms. In mice, hepsin deficiency increases adipose browning and protects from high-fat diet-induced hyperglycemia, hyperlipidemia, and obesity. Similarly, matriptase-2 deficiency increases fat lipolysis and reduces obesity and hepatic steatosis in high-fat diet-fed mice. In contrast, corin deficiency increases white adipose weights and cell sizes, suppresses adipocyte browning and thermogenic responses, and causes cold intolerance in mice. These findings highlight an important role of TTSPs in modifying cellular phenotype and function in adipose tissue. In this review, we provide a brief description about TTSPs and discuss recent findings regarding the role of hepsin, matriptase-2, and corin in regulating adipose tissue phenotype, energy metabolism, and thermogenic responses.
脂肪组织是能量代谢和体温调节中的关键器官。在病理生理条件下，脂肪组织表型受多种信号传导机制控制。II型跨膜丝氨酸蛋白酶（TTSPs）是一类锚定在细胞表面的胰蛋白酶样酶。这些蛋白酶在多种组织中发挥作用，调节诸如食物消化、水盐平衡、铁代谢、上皮完整性和听觉神经发育等生理过程。最近，TTSP家族的几个成员，即组织蛋白酶、matriptase-2和corin，已被证明通过直接激活生长因子或间接激素机制在调节脂质代谢、脂肪组织表型和产热中发挥作用。在小鼠中，组织蛋白酶缺乏会增加脂肪褐变，并预防高脂饮食诱导的高血糖、高血脂和肥胖。同样，matriptase-2缺乏会增加脂肪分解，并减轻高脂饮食喂养小鼠的肥胖和肝脂肪变性。相反，corin缺乏会增加白色脂肪重量和细胞大小，抑制脂肪细胞褐变和产热反应，并导致小鼠不耐寒。这些发现突出了TTSPs在改变脂肪组织细胞表型和功能方面的重要作用。在这篇综述中，我们简要介绍了TTSPs，并讨论了关于组织蛋白酶、matriptase-2和corin在调节脂肪组织表型、能量代谢和产热反应中作用的最新发现。
