Yan Junbin, Nie Yunmeng, Cao Jielu, Luo Minmin, Yan Maoxiang, Chen Zhiyun, He Beihui
The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou, China.
Front Cardiovasc Med. 2021 Mar 31;8:655575. doi: 10.3389/fcvm.2021.655575. eCollection 2021.
With the continuous improvement of living standards but the lack of exercise, aging-associated metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) are becoming a lingering dark cloud over society. Studies have found that metabolic disorders are near related to glucose, lipid metabolism, and cellular aging. Fibroblast growth factor 21 (FGF21), a member of the FGFs family, efficiently regulates the homeostasis of metabolism and cellular aging. By activating autophagy genes and improving inflammation, FGF21 indirectly delays cellular aging and directly exerts anti-aging effects by regulating aging genes. FGF21 can also regulate glucose and lipid metabolism by controlling metabolism-related genes, such as adipose triglyceride lipase (ATGL) and acetyl-CoA carboxylase (ACC1). Because FGF21 can regulate metabolism and cellular aging simultaneously, FGF21 analogs and FGF21 receptor agonists are gradually being valued and could become a treatment approach for aging-associated metabolic diseases. However, the mechanism by which FGF21 achieves curative effects is still not known. This review aims to interpret the interactive influence between FGF21, aging, and metabolic diseases and delineate the pharmacology of FGF21, providing theoretical support for further research on FGF21.
随着生活水平的不断提高但缺乏运动，肥胖、2型糖尿病（T2DM）和非酒精性脂肪性肝病（NAFLD）等与衰老相关的代谢性疾病正成为笼罩社会的挥之不去的阴霾。研究发现，代谢紊乱与葡萄糖、脂质代谢以及细胞衰老密切相关。成纤维细胞生长因子21（FGF21）是FGFs家族的一员，能有效调节代谢和细胞衰老的稳态。通过激活自噬基因和改善炎症，FGF21间接延缓细胞衰老，并通过调节衰老基因直接发挥抗衰老作用。FGF21还可通过控制与代谢相关的基因，如脂肪甘油三酯脂肪酶（ATGL）和乙酰辅酶A羧化酶（ACC1）来调节葡萄糖和脂质代谢。由于FGF21能同时调节代谢和细胞衰老，FGF21类似物和FGF21受体激动剂正逐渐受到重视，并可能成为治疗与衰老相关代谢性疾病的一种方法。然而，FGF21实现治疗效果的机制仍不清楚。本综述旨在解读FGF21、衰老和代谢性疾病之间的相互影响，并阐述FGF21的药理学，为进一步研究FGF21提供理论支持。
