成纤维细胞生长因子21治疗肥胖症及其相关代谢性疾病的研究进展

Research progress of fibroblast growth factor 21 in the treatment of obesity and its associated metabolic diseases

成纤维细胞生长因子(FGF)21是一类新近发现的代谢调节因子,主要由肝脏分泌,与靶组织的FGF受体(FGFR)及共受体β-klotho形成的受体复合物结合,发挥减重、降血糖、改善脂代谢以及减少组织炎性反应等作用。实验证实,外源性给予FGF21能够通过诱导能量消耗、促进脂肪分解、减少脂质合成、促进白色脂肪组织棕色化、增加脂联素水平和改善瘦素抵抗等发挥减重、改善糖脂代谢、保护胰岛和心肌细胞的作用。目前,基于FGF21的药物研发成为当前的研究热点,主要包括人FGF21类似物和FGF21受体激动剂两种,已在动物和人体试验中应用于改善肥胖症及非酒精性脂肪性肝炎、糖尿病等代谢异常相关疾病,有望成为治疗这些疾病的新药。

Fibroblast growth factor 21(FGF21)is a newly discovered metabolic regulator.It is mainly secreted by the liver and cooperates with the receptor complex composed by FGF receptor (FGFR) andβ-Klotho co-receptor in target tissue.It can reduce weight,decrease blood sugar,improve lipid metabolism and lessen tissue inflammation.Exogenous administration of FGF21 plays the role of reducing weight,improving glucolipid metabolism and protecting pancreatic islet and myocardial cells by enhancing energy consumption,promoting lipolysis,inhibiting lipogenesis,increasing browning of white adipose tissue,raising adiponectin and improving leptin resistance.At present,the research of drugs based on FGF21 has become a current hot spot,which mainly include human FGF21 analogues and FGF21 receptor agonists.They have been applied in animals and human's trials to improve obesity and related metabolic abnormalities such as nonalcoholic steatohepatitis and diabetes.They are expected to become new drugs for the treatment of these diseases.