The present review focuses on the roles and underlying mechanisms of action of hepatic nuclear factor-1 (HNF-1) in lipid metabolism and the development of lipid metabolism disorders. HNF-1 is a transcriptional regulator that can form homodimers, and the HNF-1α and HNF-1β isomers can form heterodimers. Both homo- and heterodimers recognize and bind to specific cis-acting elements in gene promoters to transactivate transcription and to coordinate the expression of target lipid-related genes, thereby influencing the homeostasis of lipid metabolism. HNF-1 was shown to restrain lipid anabolism, including synthesis, absorption, and storage, by inhibiting the expression of lipogenesis-related genes, such as peroxisome proliferator-activated receptor γ (PPARγ) and sterol regulatory element-binding protein-1/2 (SREBP-1/2). Moreover, HNF-1 enhances the expression of various genes, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), glutathione peroxidase 1 (GPx1), and suppressor of cytokine signaling-3 (SOCS-3) and negatively regulates signal transducer and activator of transcription (STAT) to facilitate lipid catabolism in hepatocytes. HNF-1 reduces hepatocellular lipid decomposition, which alleviates the progression of nonalcoholic fatty liver disease (NAFLD). HNF-1 impairs preadipocyte differentiation to reduce the number of adipocytes, stunting the development of obesity. Furthermore, HNF-1 reduces free cholesterol levels in the plasma to inhibit aortic lipid deposition and lipid plaque formation, relieving dyslipidemia and preventing the development of atherosclerotic cardiovascular disease (ASCVD). In summary, HNF-1 transcriptionally regulates lipid-related genes to manipulate intracorporeal balance of lipid metabolism and to suppress the development of lipid metabolism disorders.

本综述重点关注肝核因子-1 (HNF-1) 在脂质代谢和脂质代谢紊乱发展中的作用和潜在作用机制。HNF-1是一种转录调节因子，可以形成同源二聚体，HNF-1α和HNF-1β异构体可以形成异源二聚体。同二聚体和异二聚体都识别并结合基因启动子中的特定顺式作用元件，以反式激活转录并协调靶脂质相关基因的表达，从而影响脂质代谢的稳态。HNF-1 显示通过抑制脂肪生成相关基因的表达来抑制脂质合成代谢，包括合成、吸收和储存，例如过氧化物酶体增殖物激活受体 γ (PPARγ)和甾醇调节元件结合蛋白-1/2 (SREBP-1/2)。此外，HNF-1 增强各种基因的表达，如前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9)、谷胱甘肽过氧化物酶 1 ( GPx1 ) 和细胞因子信号传导抑制因子 3 (SOCS-3)，并负调节信号转导和转录激活因子 (STAT)促进肝细胞中的脂质分解代谢。HNF-1 减少肝细胞脂质分解，从而缓解非酒精性脂肪肝疾病 (NAFLD) 的进展。HNF-1 会损害前脂肪细胞分化以减少脂肪细胞的数量，从而阻碍肥胖的发展。此外，HNF-1 可降低血浆中的游离胆固醇水平，从而抑制主动脉脂质沉积和脂质斑块形成，缓解血脂异常并预防动脉粥样硬化性心血管疾病 (ASCVD) 的发展。总之，HNF-1 转录调节脂质相关基因以控制脂质代谢的体内平衡并抑制脂质代谢障碍的发展。