FAT/CD36, changed in unison with b-oxidation, Krebs cycle and oxidative phosphorylation proteins, but inversely to the sarcolemmal glucose transporters. The changes in substrate Moexipril HCl uptake proteins were proportional to disease severity, as an increase in cardiac hypertrophy was accompanied by decreased FAT/CD36 and increased GLUT4. This shift from FAT/CD36 to GLUT4 mirrors the metabolic shift from fatty acid to glucose metabolism that occurs with increasing hypertrophy. The fatty acid transporters have received increasing interest in recent years because of their involvement in the metabolic dysfunction occurring in heart disease, diabetes and lipotoxicity. The positive relationship between FAT/CD36, Pyriproxyfen FABPpm and H-FABP in the present study demonstrates that changes in these three transporters were co-ordinated. Their cellular location indicates they may be involved in sequential steps in the fatty acid uptake pathway, with FABPpm on the extracellular leaflet binding the fatty acid, FAT/CD36 spanning the membrane internalising the fatty acid, and H-FABP within the cytosol transporting the fatty acid away. Thus, a coordinated decrease in all three transporters would help regulate the overall process of fatty acid uptake. FAT/CD36 deficiency has been identified in some patients with hereditary hypertrophic cardiomyopathy, associated with a decreased myocardial uptake of fatty acids. In vivo measurements of fatty acid metabolism in patients with cardiac hypertrophy have shown decreases in both myocardial fatty acid uptake and oxidation. Studies have reported decreased expression of genes encoding mitochondrial fatty acid oxidation genes, including MCAD and CPT1. The relative decreases in FAT/CD36, MCAD, a-ketogluturate dehydrogenase and ATP synthase proteins in the present study demonstrates that co-ordinated changes are occurring in sequential pathways involved in fatty acid metabolism, including fatty acid uptake, b-oxidation, the Krebs cycle and oxidative phosphorylation. If, for example, downregulation of fatty acid oxidation occurred independent of a decrease in fatty acid uptake, cytosolic lipid accumulation and lipotoxicity may occur. Thus, synchronised regulation of sequential pathways would ensure deleterious intermediates did not accumulate within the cell. The changes in a-ketoglutarate dehydrogenase and ATP synthase indicate that oxidation of all mitochondrial substrates may be downregulated, not just fatty acids. This is in agreement with the decreased glutamate state 3 respiration rates measured in biopsies from failing human hearts. That the other fatty acid transporters did not display a significant relationship with downstream mitochondrial metabolic proteins was unexpected. However, this could be due to the hypothesised predominant role of FAT/CD36 in regulating the overall fatty acid uptake pathway or due to insufficient statistical power.