胃肠道糖脂转运体在代谢功能障碍相关脂肪性肝病中的研究进展

Research Progress of Gastrointestinal Glucose and Lipid Transporters in Metabolic Dysfunction-Associated Steatotic Liver Disease

摘要: 代谢功能障碍相关脂肪性肝病(metabolic dysfunction-associated steatotic liver disease, MASLD)已成为全球最常见的慢性肝病之一。胃肠道作为肝脏代谢底物输入和肠–肝信号传递的上游枢纽，其对葡萄糖、果糖、胆固醇、胆汁酸及脂肪酸的跨膜转运，与肝脂沉积、炎症反应和纤维化进展密切相关。近年来，随着MASLD/MASH命名更新、肠–肝轴研究深入及药物治疗证据不断累积，胃肠道糖脂转运体的研究内涵已由“营养吸收通道”拓展为“营养感知、代谢重编程、疾病分层与治疗靶向”的整合网络。本文围绕葡萄糖与果糖转运体、胆固醇与胆汁酸转运系统、脂肪酸转运相关蛋白3个方面，对SGLT1/SGLT2、GLUT2/GLUT5、NPC1L1、ABCG5/8、ASBT-FXR-FGF19轴、FATP、FABP及CD36等分子的研究进展进行综述，并结合近年来指南、系统评价和代表性临床试验，分析其在MASLD发生发展中的作用及转化价值。现有证据提示：SGLT2抑制剂可改善影像学脂肪变和部分非侵入性纤维化指标；GLUT5介导的果糖转运与胰岛素抵抗、肝纤维化风险及高果糖相关脂肪性肝病密切相关；NPC1L1是连接肠道胆固醇吸收与肝内胆固醇负荷的重要节点，但依折麦布对肝脂肪的直接改善作用有限；ASBT-FXR-FGF19轴是近年来胆汁酸转运研究的重要扩展；FATP5、FABP1和CD36则进一步揭示了脂毒性、炎症和纤维化与脂质递送之间的联系。未来应加强器官特异性干预、患者分层和联合治疗研究，以推动该领域由机制研究走向精准治疗。

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most prevalent chronic liver disease worldwide. As an upstream hub for nutrient delivery and gut-liver signaling, the gastrointestinal tract influences hepatic steatosis, inflammation, and fibrosis through the transmembrane transport of glucose, fructose, cholesterol, bile acids, and fatty acids. With the recent update in disease nomenclature, expansion of gut-liver axis research, and rapid accumulation of therapeutic evidence, gastrointestinal transporters should no longer be viewed merely as “absorptive channels”, but rather as an integrated network linking “nutrient sensing, metabolic reprogramming, disease stratification, and therapeutic intervention”. This review summarizes recent advances in glucose and fructose transporters, cholesterol and bile-acid transport systems, and fatty-acid transport-related proteins, with a focus on SGLT1/SGLT2, GLUT2/GLUT5, NPC1L1, ABCG5/8, the ASBT-FXR-FGF19 axis, FATP, FABP, and CD36. Recent guidelines, meta-analyses, and representative clinical trials are incorporated to evaluate their mechanistic and translational relevance in MASLD. Current evidence indicates that SGLT2 inhibitors improve imaging-based steatosis and some noninvasive fibrosis indices; GLUT5-mediated fructose transport is closely associated with insulin resistance, fibrosis risk, and fructose-driven steatotic liver disease; NPC1L1 remains a key mechanistic bridge between intestinal cholesterol absorption and hepatic cholesterol burden, although ezetimibe has limited direct benefit on liver fat; the ASBT-FXR-FGF19 pathway represents a major post-2017 expansion of bile-acid transport research; and FATP5, FABP1, and CD36 further connect lipid delivery with lipotoxicity, inflammation, and fibrosis. Future studies should prioritize organ-specific intervention, patient stratification, and combination therapy to promote precision treatment in MASLD.