代谢功能障碍相关脂肪变性肝病中的胰岛素样生长因子结合蛋白
Insulin-like growth factor binding proteins in metabolic dysfunction-associated steatotic liver disease.
摘要(中文译文)
代谢功能障碍相关脂肪变性肝病（MASLD）是一种非常普遍的疾病，从肝脂肪变性发展为脂肪性肝炎、纤维化和肝硬化。虽然疾病进展的代谢和炎症驱动因素得到了很好的认识，但新的证据表明，内分泌调节剂，包括胰岛素样生长因子结合蛋白（IGFBP），在MASLD中起着重要作用。除了作为胰岛素样生长因子（IGF）载体的典型作用外，IGFBP还通过IGF依赖性和IGF非依赖性机制充当肝脏代谢、炎症和纤维化重塑的动态调节因子。越来越多的证据表明，IGFBP1和IGFBP2通过促进脂质氧化和增加胰岛素敏感性来提供代谢保护。IGFBP3和IGFBP5具有双重作用：它们在早期抑制脂肪生成，但在纤维化过程中促进肝细胞损伤和星状细胞活化。IGFBP7是一种主要的致病性调节剂，会损害胰岛素信号传导，导致铁下垂，并促进纤维化。相比之下，IGFBP4和IGFBP6的特征仍然不太清楚。本综述将最近关于MASLD中IGFBP的机制和转化发现与最近研究积累的证据相结合，强调了它们作为疾病分期的生物标志物和干预措施的治疗靶点的潜力。
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that progresses from hepatic steatosis to steatohepatitis, fibrosis, and cirrhosis. While metabolic and inflammatory drivers of disease progression are well recognized, emerging evidence suggests that endocrine modulators, including the insulin-like growth factor binding proteins (IGFBPs), play important roles in MASLD. Beyond their canonical role as insulin-like growth factor (IGF) carriers, IGFBPs act as dynamic regulators of hepatic metabolism, inflammation, and fibrotic remodeling through both IGF-dependent and IGF-independent mechanisms. Growing evidence indicates that IGFBP1 and IGFBP2 confer metabolic protection by promoting lipid oxidation and increasing insulin sensitivity. IGFBP3 and IGFBP5 exhibit dual actions: they restrain lipogenesis at early stages but promote hepatocellular injury and stellate cell activation during fibrosis. IGFBP7 is a predominantly pathogenic modulator that impairs insulin signaling, drives ferroptosis, and fosters fibrosis. By contrast, IGFBP4 and IGFBP6 remain less well characterized. This review integrates recent mechanistic and translational findings on IGFBPs in MASLD with evidence accumulated from recent studies, highlighting their potential as biomarkers for disease staging and as therapeutic targets for interventions.
如何引用
AMA
Kuo Fang, Ji Miao, Guobin Song. Insulin-like growth factor binding proteins in metabolic dysfunction-associated steatotic liver disease.. Frontiers in endocrinology. 2026; doi:10.3389/fendo.2026.1853302.
APA
Kuo Fang, Ji Miao, Guobin Song (2026). Insulin-like growth factor binding proteins in metabolic dysfunction-associated steatotic liver disease.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1853302
GB/T 7714
Kuo Fang, Ji Miao, Guobin Song. Insulin-like growth factor binding proteins in metabolic dysfunction-associated steatotic liver disease.[J]. Frontiers in endocrinology, 2026 doi:10.3389/fendo.2026.1853302.
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