TY - JOUR

T1 - Insulin sensitivity is independent of lipid binding protein trafficking at the plasma membrane in human skeletal muscle

T2 - Effect of a 3-day, high-fat diet

AU - Jordy, Andreas Børsting

AU - Serup, Annette Karen

AU - Karstoft, Kristian

AU - Pilegaard, Henriette

AU - Kiens, Bente

AU - Jeppesen, Jacob Fuglsbjerg

N1 - CURIS 2014 NEXS 263

PY - 2014

Y1 - 2014

N2 - The aim of the present study was to investigate lipid-induced regulation of lipid binding proteins in human skeletal muscle and the impact hereof on insulin sensitivity. Eleven healthy male subjects underwent a 3-day hyper-caloric and high-fat diet regime. Muscle biopsies were taken before and after the diet intervention and giant sarcolemmal vesicles were prepared. The high-fat diet induced decreased insulin sensitivity but this was not associated with a relocation of FAT/CD36 or FABPpm protein to the sarcolemma. However, FAT/CD36 and FABPpm mRNA, but not the proteins, were up-regulated by increased fatty acid availability. This suggests a time dependency in the up-regulation of FAT/CD36 and FABPpm protein during high availability of plasma fatty acids. Furthermore, we did not detect FATP1 and FATP4 protein in giant sarcolemmal vesicles obtained from human skeletal muscle. In conclusion, this study shows that a short-term lipid-load increases mRNA content of key lipid handling proteins in human muscle. However, decreased insulin sensitivity after high-fat diet is not accompanied with relocation of FAT/CD36 or FABPpm protein to the sarcolemma. Finally, FATP1 and FATP4 protein could was located intracellularly but not at the sarcolemma in humans.

AB - The aim of the present study was to investigate lipid-induced regulation of lipid binding proteins in human skeletal muscle and the impact hereof on insulin sensitivity. Eleven healthy male subjects underwent a 3-day hyper-caloric and high-fat diet regime. Muscle biopsies were taken before and after the diet intervention and giant sarcolemmal vesicles were prepared. The high-fat diet induced decreased insulin sensitivity but this was not associated with a relocation of FAT/CD36 or FABPpm protein to the sarcolemma. However, FAT/CD36 and FABPpm mRNA, but not the proteins, were up-regulated by increased fatty acid availability. This suggests a time dependency in the up-regulation of FAT/CD36 and FABPpm protein during high availability of plasma fatty acids. Furthermore, we did not detect FATP1 and FATP4 protein in giant sarcolemmal vesicles obtained from human skeletal muscle. In conclusion, this study shows that a short-term lipid-load increases mRNA content of key lipid handling proteins in human muscle. However, decreased insulin sensitivity after high-fat diet is not accompanied with relocation of FAT/CD36 or FABPpm protein to the sarcolemma. Finally, FATP1 and FATP4 protein could was located intracellularly but not at the sarcolemma in humans.

U2 - 10.1152/ajpregu.00124.2014

DO - 10.1152/ajpregu.00124.2014

M3 - Journal article

C2 - 25163924

VL - 307

SP - R1136-R1145

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 9

ER -