Huang Zhe, Xu Aimin, Cheung Bernard M Y
Department of Medicine, 8/F Laboratory Block, Li Ka Shing Faculty of Medicine, University of Hong Kong, 21 Sassoon Road, Hong Kong, Hong Kong.
The State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, Hong Kong.
Curr Hypertens Rep. 2017 Apr;19(4):28. doi: 10.1007/s11906-017-0730-5.
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced. Chronic treatment with recombinant FGF21 reduces serum and hepatic triglyceride levels and ameliorates fatty liver in obese mice, through the suppression of the lipogenic gene, Srebp-1. FGF21 reduces hepatic cholesterol production by inhibiting Srebp-2, a transactivator of proprotein convertase subtilisin/kexin type 9 (PCSK9). LY2045319, an FGF21 analog, reduces LDL-C and triglycerides and increases HDL-C in obese human subjects with type 2 diabetes. FGF21 does not seem to lower blood pressure acutely. In rats fed with high-fructose water to induce mild hypertension, 4-week treatment with recombinant FGF21 led to normalization of systolic blood pressure and improved serum lipid profile. FGF receptors and β-Klotho are expressed on the nucleus tractus solitarii and nodose ganglion in the baroreflex afferent pathway. Moreover, FGF21 acts on the hypothalamus to release corticosterone and induces in adipocytes the production of adiponectin, an adipokine with antihypertensive activities. Therefore, FGF21 may decrease blood pressure indirectly, through its actions in the liver, brain, and adipose tissues.
成纤维细胞生长因子（FGF）21属于FGF超家族，参与细胞增殖与分化、神经发育、血管生成及代谢过程。FGF21需要β-klotho作为共受体。肝脏、脂肪组织、骨骼肌和胰腺等参与代谢的组织表达FGF21。饥饿会增加肝脏中FGF21的表达，进而在中枢发挥作用以增加肝脏糖异生。FGF21还能增加脂肪酸氧化。这在冷暴露时可能具有相关性，此时FGF21的表达会被诱导。用重组FGF21进行长期治疗可降低肥胖小鼠的血清和肝脏甘油三酯水平，并通过抑制脂肪生成基因Srebp-1改善脂肪肝。FGF21通过抑制前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）的反式激活因子Srebp-2来减少肝脏胆固醇生成。FGF21类似物LY2045319可降低2型糖尿病肥胖患者的低密度脂蛋白胆固醇（LDL-C）和甘油三酯水平，并提高高密度脂蛋白胆固醇（HDL-C）水平。FGF21似乎不会急性降低血压。在喂食高果糖水以诱导轻度高血压的大鼠中，用重组FGF21治疗4周可使收缩压恢复正常，并改善血脂谱。FGF受体和β-klotho在压力感受性反射传入通路的孤束核和结状神经节上表达。此外，FGF21作用于下丘脑以释放皮质酮，并诱导脂肪细胞产生脂联素，脂联素是一种具有降压活性的脂肪因子。因此，FGF21可能通过其在肝脏、大脑和脂肪组织中的作用间接降低血压。
