Transcriptional regulation of skeletal muscle GLUT4 by elevated long chain fatty acids

Abstract

A high-fat diet plays a role in insulin resistance and suppresses the expression of the glucose transporter 4 (GLUT4) in skeletal muscle. The objective of this study was to determine the effect of the individual long chain fatty acids, saturated or unsaturated, cis- or trans-confirmation, on transcriptional activity of the human GLUT4 promoter. We used a full-length human GLUT4 promoter with a luciferase reporter transfected into rat skeletal muscle (L6) cells. Transfected myotubes were exposed to individual long chain fatty acids (16–20 carbon), both saturated and unsaturated (one and two points of unsaturation), and 18:1 cis- and trans-confirmation. All fatty acids tested either had no effect on transcriptional activity or significantly reduced transcriptional activity. We found a decrease in transcriptional activity with two of the long-chain saturated fatty acids. Neither the cis- and trans-confirmation fatty acid regulated the transcriptional activity of the GLUT4 promoter similarly nor did the monounsaturated and polyunstaturated fatty acid regulate the transcriptional activity of the GLUT4 promoter similarly. We conclude that long chain fatty acids differentially regulate the expression of GLUT4 in muscle and any alteration by these particular fatty acids in expression of GLUT4 would result in a deleterious effect on glucose transport. This research was supported by East Carolina University.