The mesophase of parenteral fat emulsion is both substrate and inhibitor of lipoprotein lipase and hepatic lipase.
Six 10% and 20% parenteral fat emulsions were separated by centrifugation into two fractions: (1) a supernatant containing the bulk of triacylglycerols (Tg) as fat particles stabilized by phospholipids (PL); and (2) an infranatant, called mesophase, consisting essentially of PL (one third of the original PL in the 10% formula, one sixth in the 20% formula, in the case of emulsions containing 12 g PL.L-1) and small amounts of Tg and free sterols, probably in the form of liposomes. The lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the Tg-rich lipoprotein clearance, hydrolyze both types of particles, although Tg-fat particles are their preferred substrate. Inactivated serum (providing apo C-II) is needed to ensure the maximum LPL hydrolysis rate of both types of particles. It partially inhibits the HL activity on the mesophase. Substrate of the lipolytic enzymes, the mesophase, is also an inhibitor of their activity, the inhibition being directly proportional to the amount of PL contained in the mesophase. This inhibition is of uncompetitive type. For LPL, it seems that the mesophase acts on a site distinct from that of the apo C-II binding site. These results partly explain the low PL clearance after a fat emulsion infusion. But in particular, they help to explain the lower clearance of a 10% emulsion (larger PL excess) compared with a 20% emulsion (with the same amount of Tg, but less PL excess).
Lutz
O
O
Laboratoire de la Clinique Médicale A, Hôpital Civil, Strasbourg, France.
Meraïhi
Z
Z
Ferezou
J
J
Frey
A
A
Lutton
C
C
Bach
A C
AC
D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D004655:Emulsions; D007263:Infusions, Parenteral; D008049:Lipase / Q000037:antagonists & inhibitors*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology*; D010743:Phospholipids / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism / Q000493:pharmacokinetics
D004041:Dietary Fats; D004655:Emulsions; D010743:Phospholipids; D014280:Triglycerides; D008049:Lipase; D008071:Lipoprotein Lipase