成纤维细胞生长因子21在非酒精性脂肪性肝病中的应用现状与展望

金雷钢; 耿磊落; 徐爱民

doi:10.3969/j.issn.1001-5256.2021.06.006

成纤维细胞生长因子21在非酒精性脂肪性肝病中的应用现状与展望

DOI: 10.3969/j.issn.1001-5256.2021.06.006

金雷钢^{a, b, c},
耿磊落^{a, b},
徐爱民^{a, b, c, ,}

a.
香港大学生物医药技术国家重点实验室，香港特别行政区 999077
b.
香港大学内科系，香港特别行政区 999077
c.
香港大学药理与药剂系，香港特别行政区 999077

基金项目:

国家自然基金面上项目 (82070860)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：金雷钢负责收集分析资料，撰写论文；耿磊落负责论文修改；徐爱民拟定写作思路，指导文章撰写并最后定稿。

详细信息

作者简介:
金雷钢(1990—)，男，博士，主要从事代谢性疾病研究

通信作者:
徐爱民，amxu@hku.hk

中图分类号: R575.5
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- 被引次数: 0
出版历程
- 收稿日期: 2021-04-03
- 录用日期: 2021-04-13
- 出版日期: 2021-06-20

Current status and perspectives of fibroblast growth factor 21 in nonalcoholic fatty liver disease

Leigang JIN^{a, b, c},
Leiluo GENG^{a, b},
Aimin XU^{a, b, c
, ,}

a.
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China
b.
Department of Medicine, The University of Hong Kong, Hong Kong 999077, China
c.
Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong 999077, China

摘要

摘要: 成纤维细胞生长因子21(FGF21)是一种主要由肝细胞产生的分泌因子，在维持机体能量代谢平衡、调节胰岛素敏感性等过程中发挥重要作用。临床研究显示，血液FGF21在肥胖相关的非酒精性脂肪性肝病(NAFLD)患者中明显升高，是预测NAFLD发生发展的可靠生物标志物。在动物模型及NAFLD患者中，注射外源性FGF21可明显缓解该病病理进程。从FGF21的生物学特性出发，阐述其调控肝代谢及减轻肝损伤的分子作用机制，并着重讨论FGF21类似物及其受体激动剂在临床试验治疗NAFLD及非酒精性脂肪性肝炎的最新进展，以及遇到的主要问题与挑战，并展望其诊治NAFLD的应用前景。
- 成纤维细胞生长因子21 /
- 非酒精性脂肪性肝病 /
- 代谢综合征X
Abstract: Fibroblast growth factor 21 (FGF21) is a peptide hormone predominantly secreted by the liver and plays a crucial role in maintaining whole-body energy metabolism and regulating insulin sensitivity. A large number of clinical studies have demonstrated that serum FGF21 levels are increased in obese patients with non-alcoholic fatty liver disease (NAFLD), and high circulating FGF21 is a sensitive biomarker for predicting the onset and progression of NAFLD. Injection of exogenous FGF21 can effectively alleviate pathological process in both animal models and NAFLD patients. This review aims to describe the molecular mechanism underlying the hepatoprotective effects of FGF21; to summarize the current data and challenges of the clinical trials on FGF21 analogs and receptor agonists in the treatment of NAFLD and nonalcoholic steatohepatitis (NASH); and to speculate the future directions of FGF21 as a diagnosis and treatment for NAFLD.
- Fibroblast Growth Factor 21 /
- Non-alcoholic Fatty Liver Disease /
- Metabolic Syndrome X

HTML全文

图 1 FGF21调控肝脏代谢及减轻肝损伤的直接或间接作用

注：肝脏生成的FGF21通过血液循环到达机体各组织。在白色脂肪组织中，FGF21促进脂联素的生成和分泌，后者与肝脏中的脂联素受体结合，改善肝糖脂代谢；FGF21也可以通过作用于神经系统，调节肝代谢，维持机体葡萄糖稳态；另外，肝脏产生的FGF21也可以作用于肝脏本身，促进脂肪酸氧化，降低脂质合成，增加肝脏胰岛素敏感性，从而减缓肝损伤。

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