Peroxisomal and mitochondrial oxidation of fatty acids in the heart, assessed from the 13C labeling of malonyl-CoA and the acetyl moiety of citrate

We previously showed that a fraction of the acetyls used to synthesize malonyl-CoA in rat heart derives from partial peroxisomal oxidation of very long and long-chain fatty acids. The C-13 labeling ratio ( malonylCoA)/( acetyl moiety of citrate) was > 1.0 with C-13-fatty acids, which yields [C-13] acetyl-CoA in both mitochondria and peroxisomes and <1.0 with substrates, which yields [C-13] acetyl-CoA only in mitochondria. In this study, we tested the influence of C-13-fatty acid concentration and chain length on the labeling of acetyl-CoA formed in mitochondria and/or peroxisomes. Hearts were perfused with increasing concentrations of labeled docosanoate, oleate, octanoate, hexanoate, butyrate, acetate, or dodecanedioate. In contrast to the liver, peroxisomal oxidation of 1-C-13- fatty acids in heart does not form [1-C-13] acetate. With [1-C-13] docosanoate and [ 1,12(13)C(2)] dodecanedioate, malonyl-CoA enrichment plateaued at 11 and 9%, respectively, with no detectable labeling of the acetyl moiety of citrate. Thus, in the intact rat heart, docosanoate and dodecanedioate appear to be oxidized only in peroxisomes. With [1-C-13] oleate or [1-C-13] octanoate, the labeling ratio >1 indicates the partial peroxisomal oxidation of oleate and octanoate. In contrast, with [3-C-13] octanoate, [1-C-13] hexanoate, [1-C-13] butyrate, or [1,2-C-13(2)] acetate, the labeling ratio was <0.7 at all concentrations. Therefore, in rat heart, ( i) n-fatty acids shorter than 8 carbons do not undergo peroxisomal oxidation, ( ii) octanoate undergoes only one cycle of peroxisomal beta-oxidation, ( iii) there is no detectable transfer to the mitochondria of acetyl-CoA from the cytosol or the peroxisomes, and ( iv) the capacity of C-2 - C-18 fatty acids to generate mitochondrial acetyl-CoA decreases with chain length.