Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, China.
Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Int J Mol Sci. 2023 Feb 26;24(5):4583. doi: 10.3390/ijms24054583.
Nonalcoholic fatty liver disease (NAFLD), a chronic condition associated with metabolic dysfunction and obesity, has reached epidemic proportions worldwide. Although early NAFLD can be treated with lifestyle changes, the treatment of advanced liver pathology, such as nonalcoholic steatohepatitis (NASH), remains a challenge. There are currently no FDA-approved drugs for NAFLD. Fibroblast growth factors (FGFs) play essential roles in lipid and carbohydrate metabolism and have recently emerged as promising therapeutic agents for metabolic diseases. Among them, endocrine members (FGF19 and FGF21) and classical members (FGF1 and FGF4) are key regulators of energy metabolism. FGF-based therapies have shown therapeutic benefits in patients with NAFLD, and substantial progress has recently been made in clinical trials. These FGF analogs are effective in alleviating steatosis, liver inflammation, and fibrosis. In this review, we describe the biology of four metabolism-related FGFs (FGF19, FGF21, FGF1, and FGF4) and their basic action mechanisms, and then summarize recent advances in the biopharmaceutical development of FGF-based therapies for patients with NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种与代谢功能障碍和肥胖相关的慢性疾病，在全球范围内已达到流行程度。虽然早期的 NAFLD 可以通过生活方式改变来治疗，但晚期肝病理如非酒精性脂肪性肝炎（NASH）的治疗仍然是一个挑战。目前尚无 FDA 批准的 NAFLD 药物。成纤维细胞生长因子（FGFs）在脂质和碳水化合物代谢中发挥着重要作用，最近已成为代谢性疾病有前途的治疗药物。其中，内分泌成员（FGF19 和 FGF21）和经典成员（FGF1 和 FGF4）是能量代谢的关键调节剂。基于 FGF 的治疗方法已在 NAFLD 患者中显示出治疗益处，并且最近在临床试验中取得了重大进展。这些 FGF 类似物在缓解脂肪变性、肝脏炎症和纤维化方面非常有效。在这篇综述中，我们描述了四种与代谢相关的 FGF（FGF19、FGF21、FGF1 和 FGF4）的生物学特性及其基本作用机制，然后总结了基于 FGF 的治疗方法在治疗 NAFLD 患者方面的生物制药开发的最新进展。
