School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Ke xue Avenue, Zhengzhou, Henan 450001, China P.R.
Key Laboratory of Animal Ecology and Conservation Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China P.R.
Benef Microbes. 2020 Feb 19;11(1):67-78. doi: 10.3920/BM2019.0093. Epub 2019 Dec 17.
Fibroblast growth factor 21 (FGF21), a metabolism regulator, has an important effect on metabolic diseases, such as obesity and diabetes. It is also expressed in mice, and the murine source has high homology with human FGF21. Recently, it has been extensively studied and has become a potential drug target for the treatment of metabolic diseases. As it is a protein-based hormone, FGF21 cannot be easily and quickly absorbed into the blood through oral administration. Moreover, it has a 0-2 h half-life , as shown in a previous study, thus its efficacy lasts for a short period of time when used to treat metabolic diseases, limiting its clinical applications. To avoid these limitations, we used , a food-grade bacterium, as the host to express FGF21. It could be used successfully for the expression and long-term effect of FGF21 . Instead of antibiotic resistance genes, the LacF gene was used as a selection marker in the NZ3900/PNZ8149 expression system, which is safe and could reduce the antibiotic resistance crisis. In this study, we a constructed human FGF21 expressing strain and administered it to Db/Db mice by gavage. Compared with the control group, the body weight of mice in the experimental group was significantly reduced, and the overall homeostasis was improved in mice treated with human FGF21. Moreover, the activity of brown adipose tissue was enhanced. These results revealed that oral administration of FGF21 through heterologous expression in appears to be an effective approach for its clinical application.
成纤维细胞生长因子 21（FGF21）是一种代谢调节剂，对肥胖症和糖尿病等代谢性疾病具有重要作用。它在小鼠中也有表达，并且与人类 FGF21 具有高度同源性。最近，它已经得到了广泛的研究，并成为治疗代谢性疾病的潜在药物靶点。由于它是一种基于蛋白质的激素，FGF21 不能通过口服轻易且快速地被吸收到血液中。此外，它的半衰期为 0-2 小时，如之前的研究所示，因此当用于治疗代谢性疾病时，其疗效持续时间较短，限制了其临床应用。为了避免这些限制，我们使用一种食品级细菌作为宿主来表达 FGF21。它可以成功地用于 FGF21 的表达和长期效果。在 NZ3900/PNZ8149 表达系统中，我们使用 LacF 基因代替抗生素抗性基因作为选择标记，这是安全的，可以减少抗生素抗性危机。在这项研究中，我们构建了表达人 FGF21 的菌株，并通过灌胃将其施用于 Db/Db 小鼠。与对照组相比，实验组小鼠的体重明显减轻，接受人 FGF21 治疗的小鼠整体内稳态得到改善，棕色脂肪组织的活性增强。这些结果表明，通过异源表达口服给予 FGF21 似乎是其临床应用的一种有效方法。
