Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle

Abstract

OBJECTIVE: It has been reported that an increased availability of free fatty acids (NEFA) not only interferes with glucose utilization in insulin-dependent tissues, but may also result in an uncoupling effect of heart metabolism. We aimed therefore to investigate the effect of an increased availability of NEFA on gene expression of proteins involved in transmembrane fatty acid (FAT=CD36) and glucose (GLUT4) transport and of the uncoupling proteins UCP2 and 3 at the heart and skeletal muscle level. STUDY DESIGN: Euglycemic hyperinsulinemic clamp was performed after 24 h Intralipid 1 plus heparin or saline infusion in lean Zucker rats. Skeletal and heart muscle glucose utilization was calculated by 2-deoxy-[1-3 H]-D-glucose technique. Quantification of FAT=CD36, GLUT4, UCP2 and UCP3 mRNAs was obtained by Northern blot analysis or RT-PCR. RESULTS: In Intralipid 1 plus heparin infused animals a significant decrease in insulin-mediated glucose uptake was observed both in the heart (22.62 AE 2.04 vs 10.37 AE 2.33 ng=mg=min; P < 0.01) and in soleus muscle (13.46 AE 1.53 vs 6.84 AE 2.58 ng=mg=min; P < 0.05). FAT=CD36 mRNA was significantly increased in skeletal muscle tissue ( þ 117.4 AE 16.3%, P < 0.05), while no differences were found at the heart level in respect to saline infused rats. A clear decrease of GLUT4 mRNA was observed in both tissues. The 24 h infusion of fat emulsion resulted in a clear enhancement of UCP2 and UCP3 mRNA levels in the heart (99.5 AE 15.3 and 80 AE 4%) and in the skeletal muscle (291.5 AE 24.7 and 146.9 AE 12.7%). CONCLUSIONS: As a result of the increased availability of NEFA, FAT=CD36 gene expression increases in skeletal muscle, but not at the heart level. The augmented lipid fuel supply is responsible for the depression of insulin-mediated glucose transport and for the increase of UCP2 and 3 gene expression in both skeletal and heart muscle.

AMP-Activated Protein Kinase Activation by 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) Inhibits Palmitate-Induced Endothelial Cell Apoptosis Through Reactive Oxygen Species Suppression

“…Interestingly, the present study showed that palmitate also increased UCP2 protein levels. In accordance with our results, the mRNA level of UCP2 is increased by fatty acids in INS-1 cells (16) and by lipid infusion in the heart and skeletal muscle of Zucker rats (22). UCP2 increases to accommodate ROS production compensatively (23).…”

SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARΔ expression in mice

“…GLUT1 is primarily responsible for noninsulin-stimulated glucose uptake (basal), whereas GLUT4 is the insulin-responsive glucose transported in skeletal muscle. It is unclear how SCD1 overexpression impacts GLUT1 and GLUT4 expressions; however, it has been reported that long-chain n-3 PUFAs increase GLUT1 expression ( 34 ) and oleate reduces GLUT4 expression ( 35 ).…”

Chronic Post-Exercise Lactate Administration with Endurance Training Increases Glycogen Concentration and Monocarboxylate Transporter 1 Protein in Mouse White Muscle

“…On the other hand, lactate administration did not change the expression of other substrate transporters; namely GLUT4 and FAT/CD36. Infusion of several energy substrates can change substrate transporter expression because of the selection of substrate utilization (17,34). Lombardi et al reported that hyperlactatemia for 24 h decreases GLUT4 mRNA and protein expression in muscle (17).…”