The fascinating and elusive life of cardiac fatty acids

Abstract

This editorial refers to ‘Second window of preconditioning normalizes palmitate use for oxidation and improves function during low-flow ischaemia’ by R.K. Kudej et al ., pp. 394–400, this issue. Kudej et al. 1 attempted to elucidate the role of fatty acids (FAs) in the second window of protection of the chronically underperfused myocardium. Using the in vivo conscious swine heart model, they elegantly showed that ischaemic preconditioning resulted in less severe thinning of the left ventricular (LV) wall 24h after the onset of ischaemia. The improved mechanical function of the ischaemic region was not due to changes in residual blood flow and, hence, increased supply of oxygen. The contribution of FAs to cardiac oxidative ATP production was estimated by infusion of 13C-palmitate and subsequent in vitro NMR analysis of palmitate-derived acetyl-CoA. The contribution of FA to oxidative energy production declined in the ischaemic LV wall accompanied by decreased malonyl-CoA levels in the ischaemic subendocardium. Interestingly, preconditioning substantially enhanced the relative contribution of FA oxidation to oxidative energy production in association with a three-fold increase in malonyl-CoA concentration. The study of Kudej et al. 1 deserves special attention especially for its iconoclastic message. Two important paradigms concerning cardiac FA utilization read that first, myocardial FA oxidation is detrimental under challenging conditions2,3 and, secondly, cardiac FA oxidation is controlled by malonyl-CoA, in that elevated malonyl-CoA levels are inhibitory.4,5 The present study, …