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It is finally emerging that TAGs are indeed major providers of cardiac energy; furthermore, alterations in myocardial TAG utilisation are clearly associated with impaired cardiac function. However, outstanding questions remain, including the teleological role of VLDL as a FA carrier and NEFA substitute (i.e. VLDL as a metabolic signal), the regulation of myocardial LPL activity in relation to metabolic (and particularly plasma TAG) status, the possibility of differential uptake pathways and intracellular channelling of FAs from different sources (NEFA; CM-TAG; VLDL-TAG), together with the requirement for incoming FAs to cycle through mTAG before oxidation. In particular, defining the precise mechanism(s) of myocellular FA assimilation, together with the extent to which TGRLP-derived FAs contribute to mTAG pool turnover, compared to the
requirement of NEFA to cycle through mTAG (hence putative intracellular FA channelling streams) remains a challenge.
Acknowledgements:
This work was supported by the British Heart Foundation (BHF).
Conflicts of interest:
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Figure legends:
Figure 1. Utilisation of triacylglycerol (TAG) by the cardiomyocyte. Triacylglycerol is available for -oxidation from exogenous supply (CM: chylomicrons; VLDL: very-low-density
TAG ts. Current
controversies include (1) the degree to which fatty acid (FA) for oxidation is supplied from these various sources, in competition with non-esterified FA (NEFA), in the normal and diseased heart (2) the respective importance of lipoprotein receptor (VLDL-R)-mediated and LPL-mediated exogenous TAG uptake (3) the specific uptake route for FA derived from lipoprotein lipase (LPL)-
TAG NEFA - FA
the sarcolemma), and whether these are shared or separate (4) the existence of distinct
intracellular FA pools derived from the various FA sources and uptake mechanisms (5) the extent to which intracellular FAs must be obligatorily cycled through intracellular mTAG prior to
utilisation as respiratory fuel, or signalling and structural functions. Lipid droplet and mitochondria are in close anatomical and functional proximity. EC: endothelial cell; DAG: diacylglycerol; GPAT: glycerol-phosphate acyltransferase; DGAT: diacylglycerol acyltransferase; ATGL: adipose
triacylglycerol lipase; PLIN5: perilipin-5; PPAR: peroxisome proliferator-activated receptor; VLDLR: VLDL-receptor; FATP: fatty acid transport protein; FAT: fatty acid translocase; FABP: fatty acid binding protein.
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