Increased FAT (fatty acid translocase)/CD36-mediated long-chain fatty acid uptake in cardiac myocytes from obese Zucker rats

Disturbed cardiac lipid homoeostasis in obesity is regarded as a key player in the development of cardiovascular diseases. In this study, we show that FAT (fatty acid translocase)/CD36-mediated LCFA (long-chain fatty acid) uptake in cardiac myocytes from young adult obese Zucker rats is markedly increased, but insensitive to insulin. Basal and insulin-induced glucose uptake rates in these myocytes are not changed, suggesting that during the development from obesity to hyperglycaemic Type II diabetes, alterations in cardiac LCFA uptake precede alterations in cardiac glucose uptake.

Download Full-text

Arsenite Modulates Cardiac Substrate Preference by Translocation of GLUT4, But Not CD36, Independent of Mitogen-Activated Protein Kinase Signaling

Endocrinology ◽

10.1210/en.2006-0849 ◽

2006 ◽

Vol 147 (11) ◽

pp. 5205-5216 ◽

Cited By ~ 9

Author(s):

Joost J. F. P. Luiken ◽

Iman Momken ◽

Daphna D. J. Habets ◽

Mohammed El Hasnaoui ◽

Will A. Coumans ◽

...

Keyword(s):

Fatty Acid ◽

Glucose Uptake ◽

P38 Mapk ◽

Fatty Acid Uptake ◽

Chain Fatty Acid ◽

Acid Uptake ◽

Long Chain Fatty Acid ◽

P70 S6k ◽

Long Chain ◽

Stimulation Of

The protein thiol-modifying agent arsenite, a potent activator of stress signaling, was used to examine the involvement of MAPKs in the regulation of cardiac substrate uptake. Arsenite strongly induced p38 MAPK phosphorylation in isolated rat cardiac myocytes but also moderately enhanced phosphorylation of p42/44 ERK and p70 S6K. At the level of cardiomyocytic substrate use, arsenite enhanced glucose uptake dose dependently up to 5.1-fold but failed to stimulate long-chain fatty acid uptake. At the substrate transporter level, arsenite stimulated the translocation of GLUT4 to the sarcolemma but failed to recruit CD36 or FABPpm. Because arsenite did not influence the intrinsic activity of glucose transporters, GLUT4 translocation is entirely responsible for the selective increase in glucose uptake by arsenite. Moreover, the nonadditivity of arsenite-induced glucose uptake and insulin-induced glucose uptake indicates that arsenite recruits GLUT4 from insulin-responsive intracellular stores. Inhibitor studies with SB203580/SB202190, PD98059, and rapamycin indicate that activation of p38 MAPK, p42/44 ERK, and p70 S6K, respectively, are not involved in arsenite-induced glucose uptake. In addition, all these kinases do not play a role in regulation of cardiac glucose and long-chain fatty acid uptake by insulin. Hence, arsenite’s selective stimulation of glucose uptake appears unrelated to its signaling actions, suggesting that arsenite acts via thiol modification of a putative intracellular protein target of arsenite within insulin-responsive GLUT4-containing stores. Because of arsenite’s selective stimulation of cardiac glucose uptake, identification of this putative target of arsenite within the GLUT4-storage compartment may indicate whether it is a target for future strategies in prevention of diabetic cardiomyopathy.

Download Full-text

Electrostimulation enhances FAT/CD36-mediated long-chain fatty acid uptake by isolated rat cardiac myocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.4.e704 ◽

2001 ◽

Vol 281 (4) ◽

pp. E704-E712 ◽

Cited By ~ 36

Author(s):

J. J. F. P. Luiken ◽

J. Willems ◽

G. J. van der Vusse ◽

J. F. C. Glatz

Keyword(s):

Fatty Acid ◽

Cardiac Myocytes ◽

Fatty Acid Uptake ◽

Chain Fatty Acid ◽

Acid Uptake ◽

Long Chain Fatty Acid ◽

Palmitate Uptake ◽

Rat Cardiac Myocytes ◽

Long Chain

We investigated palmitate uptake and utilization by contracting cardiac myocytes in suspension to explore the link between long-chain fatty acid (FA) uptake and cellular metabolism, in particular the role of fatty acid translocase (FAT)/CD36-mediated transsarcolemmal FA transport. For this, an experimental setup was developed to electrically stimulate cardiomyocytes in multiple parallel incubations. Electrostimulation at voltages ≥170 V resulted in cellular contraction with no detrimental effect on cellular integrity. At 200 V and 4 Hz, palmitate uptake (measured after 3-min incubation) was enhanced 1.5-fold. In both quiescent and contracting myocytes, after their uptake, palmitate was largely and rapidly esterified, mainly into triacylglycerols. Palmitate oxidation (measured after 30 min) contributed to 22% of palmitate taken up by quiescent cardiomyocytes and, after stimulation at 4 Hz, was increased 2.8-fold to contribute to 39% of palmitate utilization. The electrostimulation-mediated increase in palmitate uptake was blocked in the presence of either verapamil, a contraction inhibitor, or sulfo- N-succinimidyl-FA esters, specific inhibitors of FAT/CD36. These data indicate that, in contracting cardiac myocytes, palmitate uptake is increased due to increased flux through FAT/CD36.

Download Full-text