Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart.
OBJECTIVE
Cardiac fatty acid uptake occurs predominantly via sarcolemmal transporter proteins; fatty acid translocase (FAT/CD36), plasma membrane fatty acid binding protein (FABPpm) and fatty acid transporter proteins (FATP) 1 and 6. We hypothesised that levels of the fatty acid transporters would be reduced in the chronically infarcted rat heart, in parallel with reduced dependence on fatty acid utilisation.


RESULTS
In vivo left ventricular ejection fractions, measured using echocardiography, were 36% lower in rats six months after coronary artery ligation than in sham-operated control rats. In isolated, perfused, infarcted hearts, 3H-palmitate oxidation was 30% lower, and correlated with in vivo ejection fractions. As myocardial lipid incorporation was also reduced by 25%, total palmitate utilisation was 29% lower in the infarcted rat heart. The protein levels of the cardiac fatty acid transporters were reduced in the infarcted rat heart; FAT/CD36 by 36%, FABPpm by 12%, FATP6 by 21% and FATP1 by 26%, and the cytosolic fatty acid binding protein (cFABP) was 47% lower than in sham-operated rat hearts. Fatty acid transporter levels correlated with both palmitate oxidation rates and cardiac ejection fractions.


CONCLUSIONS
Reductions in fatty acid oxidation and lipid incorporation rates were accompanied by downregulation of the cardiac fatty acid transporters. The metabolic shift away from fatty acid utilisation was proportional to the degree of functional impairment in the chronically infarcted rat heart.
Heather
Lisa C
LC
Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
Cole
Mark A
MA
Lygate
Craig A
CA
Evans
Rhys D
RD
Stuckey
Daniel J
DJ
Murray
Andrew J
AJ
Neubauer
Stefan
S
Clarke
Kieran
K
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D018955:CD36 Antigens / Q000032:analysis; D002950:Citrate (si)-Synthase / Q000032:analysis; D004452:Echocardiography; D050612:Fatty Acid Transport Proteins / Q000032:analysis* / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000032:analysis; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume
D015415:Biomarkers; D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; C515999:Got2 protein, rat; D010168:Palmitates; C493570:Slc27a1 protein, rat; D002950:Citrate (si)-Synthase