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

• Published in: Nutrition research (New York, N.Y.) Vol. 24; no. 5; pp. 321 - 336
• Main Authors: Reimer, Raylene A, Leone-Vautravers, Patricia, Zbinden, Irène, Harris, Curtis C, Pfeifer, Andrea M.A, Macé, Katherine
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2004; Elsevier Science
• Subjects: binding capacity; binding proteins; Biological and medical sciences; cell culture; cell lines; Fatty acid synthase; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; gene expression regulation; glucose; glucose 6-phosphate; glucose transporter type 2 (GLUT2); glucose transporters; GLUT2; Hepatocyte cell line; hepatocytes; humans; insulin secretion; Lipogenesis; messenger RNA; nutrition-genotype interaction; transcription (genetics); transcription factors; triacylglycerols; Triglyceride; triiodothyronine; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Hepatocyte cell line; GLUT2; Fatty acid synthase; Lipogenesis; Triglyceride; Human; Acyltransferases; Vertebrata; Cell line; Mammalia; Hepatocyte; Digestive system; Enzyme; Liver; Transferases; Glucose; Fatty-acid synthase
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2004.01.002

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 (T 3). 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.