转录因子EB在调控脂质代谢中的研究进展

The research advances of transcription factor EB in the regulation of lipid metabolism

摘要:

转录因子EB(TFEB)属于小眼畸形相关转录因子(MiTF/TFE)家族,是溶酶体功能和自噬的主要调节因子,其通过调节溶酶体内脂质降解、脂肪酸β氧化以及胞内胆固醇流出等途径在调节脂质代谢过程中发挥重要作用。TFEB主要通过介导自噬以及脂质代谢相关因子的表达抑制非酒精性脂肪性肝病和肥胖症的发生,另外通过抑制巨噬细胞和血管平滑肌细胞内脂质蓄积而抑制泡沫细胞的形成延缓动脉粥样硬化的进展,还可通过促进脂噬降低脂质积累及其诱导的胰岛素抵抗与β细胞衰竭进而缓解糖尿病脂质代谢紊乱。总之,TFEB在脂质代谢过程及脂质代谢紊乱相关疾病中发挥关键作用,并可在临床上作为潜在的干预靶点以纠正体内脂质代谢紊乱。

Abstract:

Transcription factor EB (TFEB), which belongs to the microphthalmia/transcription factor E (MiTF/TFE) family, is mainly functioned as regulator involved in regulating lysosomal function and autophagy. It plays an important role in lipid metabolism via modulating lysosomal lipid degradation, mitochondrial β-oxidation of fatty acid, and intracellular cholesterol efflux. TFEB inhibits the development of metabolic associated fatty liver disease (MAFLD) and obesity by regulating the autophagy and the expression of lipid metabolism-related genes. Additionally, it prevents the formation of foam cell from macrophages and vascular smooth muscle cells by restraining lipid accumulation, thereby attenuating the progression of atherosclerosis. TFEB promotes lipophagy to relieve lipid accumulation and lipid accumulation-induced insulin resistance, and β-cell failure, deferring diabetes-related lipid metabolic disorders. In summary, TFEB plays a key role in lipid metabolism and associated lipid disorder diseases, and serves as a potential clinical target to correct lipid dysmetabolism in vivo.