Abstract: SREBP1c is a key regulator of de novo synthesis and intracellular transport of long-chain fatty acids (LCFAs). In this study, the potential relationship between disruption of the synthesis /transport of LCFAs and non-alcoholic fatty liver disease (NAFLD), which was axially regulated by SREBP1c-ACCα/FAS and SREBP1c-FABPs, was investigated. The adenovirusAd-SREBP1c was prepared for mediating the overexpression of SREBP1c, and the intracellular triglyceride (TG) content was measured by enzymatic assay followed by transfection of HepG2 cells with Ad-SREBP1c. The transcription and translation levels of ACCα, FAS, FABP3 and FABP4 were measured by RT-PCR and Western blot respectively. Ad-SREBP1c virus titer was 1.6×109GFU/mL. The transcription and translation levels of SREBP1 were enhanced by 89.73-fold (P<0.01) and 7.27-fold (P<0.01), respectively, 24 h after transfection in HepG2 cells mediated by Ad-SREBP1. The mRNA levels of ACCα and FAS for downstream LCFAs synthesis were increased by 1.55-fold (P<0.01) and 3.42-fold (P<0.01), respectively, and with increasement each by 1.23-fold (P<0.05) and 1.43-fold (P<0.01) in protein expression levels. The FABP3 mRNA and protein levels were elevated by 4.03-fold (P<0.01) and 2.06-fold (P<0.01) respectively, while no significant change was observed in FABP4. Meanwhile, intracellular TG contents of HepG2 cells of 24 h and 48 h after transfection by Ad-SREBP1c were increased by 1.24-fold (P<0.05) and 2.41-fold (P<0.01), respectively. SREBP1c-ACCα/FAS could axially regulate the de novo synthesis of LCFAs, and SREBP1c-FABP3 could axially mediate the intracellular transport of LCFAs at the same time, which was probably the key mechanism contributing to the development of NAFLD due to cytosolic ectopic lipid deposition.

Key words: non-alcoholic fatty liver disease (NAFLD), sterol regulatory element binding protein 1c (SREBP1c), ACCα/FAS, FABP3