Phospholipid-rich particles in commercial parenteral fat emulsions. An overview

In parenteral nutrition, the infusion of a fat EMU supplies both concentrated energy and covers the essential fatty acid requirements, the basic objective being to mimic as well as possible the input of chylomicrons into the blood. This objective is well met by the TAGRP of the EMU, which behave as true chylomicrons. However, commercial EMU also contain an excess of emulsifier in the form of PLRP. The number of these PLRP depends directly on the PL/TAG ratio of the EMU. They differ from the TAGRP by their composition (PL vs TAG and PL), their structure (PL in bilayer versus monolayer), and their granulometry (mean diameter 70-100 nm for PL vs 200-500 nm). The metabolic fate of the PLRP is similar in several ways to that of the TAGRP: exchanges of PL with the PL of the different cellular membranes and of the lipoproteins; captation of free CH from these same structures; and enrichment in apolipoproteins. However, because the TAGRP are the preferred substrates of the lipolytic enzymes, their clearance is much more rapid (half-life < 1 h) than that of the PLRP. As the infusion is continued, the PLRP end up accumulating and being transformed into LP-X (free CH/PL = 1; half-life of several days). As soon as the EMU is infused, the PLRP enter into competition with the TAGRP, in the lipolysis process as well as for sites of binding and for catabolism. The sites for catabolism of the two types of PAR are not the same: adipose tissues and muscles utilize the fatty acids and monoacylglycerols released by the lipolysis of the TAGRP; hepatocytes take up their remnants; the RES and the hepatocytes participate in the catabolism of the PLRP and the LP-X. Thus, prolonged infusion of EMU rich in PLRP leads to a hypercholesterolemia, or at least a dyslipoproteinemia, due to elevated LP-X, associated with a depletion of cells in CH, stimulating thus tissue cholesterogenesis. However, parenteral nutrition has evolved towards the utilization of EMU with a low PL/TAG ratio (availability of 30% formula) and less rapid delivery. For these reasons, the hypercholesterolemias that used to be observed with the 10% EMU have become much less spectacular or have even disappeared. It is interesting to note that patients on prolonged TPN, in particular those with a short small intestine, have weak cholesterolemia, reflecting a lowering of HDL and LDL not masked by elevated LP-X. At present, it seems difficult to produce sufficiently stable parenteral EMU devoid of PLRP. Notwithstanding, all the observations made since the introduction of the EMU in TPN are in favour of the use of PLRP-poor EMU. It is clear that the 10% formulas, and generally those with a PL/TAG ratio of 12/100, are ill-advised, especially in patients with a retarded clearance of circulating lipids.