Dysregulation of fatty acid synthase mRNA in immortalized human hepatocyte cell lines in response to high glucose and the absence of GLUT2

Abstract 

The lipogenic pathway has been extensively studied in rodent hepatocytes but poorly studied in human cells. This study examined the effect of glucose and hormones on fatty acid synthase (FAS) gene expression and intracellular lipid synthesis in a human hepatocyte cell line (T-9A4 cells). In low passage cells expressing glucose transporter type 2 (GLUT2) mRNA, FAS mRNA expression and triacylglycerol (TAG) synthesis increased in response to glucose and the presence of insulin and triiodothyronine (T₃). With increasing passages, the cells no longer expressed the GLUT2 gene, and levels of FAS mRNA were consistently elevated compared to GLUT2 (+) cells. Triglyceride synthesis was also consistently higher in the GLUT2 (−) cells. Glucose-6-phosphate (G-6-P) was constitutively high in GLUT2 (−) cells but increased in response to glucose in GLUT2 (+) cells. In the absence of GLUT2, glucose may be trapped in cells, continuously fueling the generation of G-6-P or subsequent metabolic intermediates that promote FAS gene transcription.

Keywords:  Lipogenesis, Fatty acid synthase, GLUT2, Hepatocyte cell line, Triglyceride