Liu Mi, Deng Mokan, Su Jiahui, Lin Yu, Jia Zhanjun, Peng Kexin, Wang Fei, Yang Tianxin
Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China.
Department of Medicine and Veterans Affairs Medical Center, University of Utah, Salt Lake City, Utah.
Physiol Rep. 2018 Jul;6(13):e13630. doi: 10.14814/phy2.13630.
Hydrogen sulfide (H S) is recognized as a novel gasotransmitter involved in the regulation of nervous system, cardiovascular functions, inflammatory response, gastrointestinal system, and renal function. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are the major enzymes responsible for H S production through desulfuration reactions. H S is reported to play a protective role in both high-fat diet (HFD)-induced obese and diabetic mice. However, the synthesizing enzyme involved is not clearly elucidated. The current study was aimed to investigate the regulation of CBS and CSE in different tissues including the kidney, liver, and epididymal fat in C57BL/6 mice after a HFD (60% kcal fat) for 24 weeks. The protein and mRNA expression of CBS was specifically decreased in the kidney while CSE remained unchanged, which was further confirmed in db/db mice. In the liver, CSE expression was downregulated after HFD accompanied with unchanged CBS. Moreover, CSE expression was even upregulated in epididymal fat. The specific downregulation of renal CBS may contribute to decreased H S production, which could be a pathogenic mechanism of obesity. Increased CSE/H S pathway in epididymal fat possibly resulted in impaired glucose uptake and aggravated insulin resistance. In conclusion, our results revealed that CBS was selectively downregulated in both diet and gene-induced obesity models.
硫化氢（H₂S）被认为是一种新型气体信号分子，参与调节神经系统、心血管功能、炎症反应、胃肠道系统和肾功能。胱硫醚β-合酶（CBS）和胱硫醚γ-裂解酶（CSE）是通过脱硫反应产生H₂S的主要酶。据报道，H₂S在高脂饮食（HFD）诱导的肥胖和糖尿病小鼠中均发挥保护作用。然而，其中涉及的合成酶尚不清楚。本研究旨在探讨C57BL/6小鼠在24周高脂饮食（60%千卡脂肪）后，肾脏、肝脏和附睾脂肪等不同组织中CBS和CSE的调节情况。CBS的蛋白质和mRNA表达在肾脏中特异性降低，而CSE保持不变，这在db/db小鼠中得到进一步证实。在肝脏中，高脂饮食后CSE表达下调而CBS不变。此外，附睾脂肪中CSE表达甚至上调。肾脏中CBS的特异性下调可能导致H₂S产生减少，这可能是肥胖的致病机制。附睾脂肪中CSE/H₂S途径增加可能导致葡萄糖摄取受损和胰岛素抵抗加重。总之，我们的结果表明，在饮食和基因诱导的肥胖模型中，CBS均被选择性下调。
