Structural and compositional changes in very low density lipoprotein triacylglycerols during basal lipolysis.
Triacylglycerols secreted by liver and carried by very low density lipoprotein (VLDL) are hydrolysed in circulation by lipoprotein and hepatic lipases. These enzymes have been shown to have positional and fatty acid specificity in vitro. If there were specificity in basal lipolysis in vivo, triacylglycerol compositions of circulating and newly secreted VLDL would be different. To study this we compared the composition of normal fasting VLDL triacylglycerol of Wistar rats to that obtained after blocking lipolysis by Triton WR1339, which increased plasma VLDL triacylglycerol concentration about 4.7-fold in 2 h. Analyses of molecular species of sn-1,2- and sn-2,3-diacylglycerol moieties and stereospecific triacylglycerol analysis revealed major differences between the groups in the VLDL triacylglycerol composition. In nontreated rats, the proportion of 16:0 was higher and that of 18:2n-6 lower in the sn-1 position. The proportion of 14:0 was lower in all positions and that of 18:0 was lower in the sn-1 and sn-3 positions in nontreated rats whereas the proportions of 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3 were higher in the sn-1 and lower in the sn-2 position. These results suggest that the fatty acid of the sn-1 position is the most decisive factor in determining the sensitivity for hydrolysis of the triacylglycerol. In addition, triacylglycerol species with highly unsaturated fatty acids in the sn-2 position also favoured hydrolysis. The in vivo substrate specificity followed only partly that obtained in in vitro studies indicating that the nature of molecular association of fatty acids in natural triacylglycerol affects its susceptibility to lipolysis. To conclude, our results indicate that preferential basal lipolysis leads to major structural differences between circulating and newly secreted VLDL triacylglycerol. These differences extend beyond those anticipated from analysis of total fatty acids and constitute a previously unrecognized feature of VLDL triacylglycerol metabolism.
Agren
Jyrki J
JJ
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada. Jyrki.Agren@uku.fi
Ravandi
Amir
A
Kuksis
Arnis
A
Steiner
George
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003902:Detergents / Q000494:pharmacology; D004075:Diglycerides / Q000737:chemistry; D005227:Fatty Acids / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014280:Triglycerides / Q000737:chemistry*; D014520:Urethane / Q000737:chemistry
D003902:Detergents; D004075:Diglycerides; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D014280:Triglycerides; D014520:Urethane; D011092:Polyethylene Glycols; D008049:Lipase; C016811:tyloxapol