Anomalous lipoproteins in obese Zucker rats

Aims: Obesity is characterized by dislipoproteinaemia with increased choles terol and triacylglycerol levels and lower chylomicra disposal rates. We st udied here whether these alterations were related to lipoprotein number and /or size and composition. Methods: Plasma from lean and obese Zucker rats was fractionated into lipop rotein classes (chylomicra, very low density lipoprotein (VLDL), low densit y lipoprotein (LDL) and high density lipoprotein (HDL)) by differential cen trifugation. The apoprotein and lipid composition of each fraction were mea sured. Lipoprotein particle size was estimated by dynamic light scattering and used to tabulate the mean diameter and volume of lipoprotein micelles, Particle mass was calculated from the density and volume. The mass of lipid s and protein in each fraction/ml of plasma allowed the estimation of mean particle concentration and then the number of molecules of lipid and protei n/unit of lipoprotein micelle. Results: A large part of hyperlipidaemia of obese rats is due to the accumu lation of chylomicra: 1.3 +/- 0.2 mg/ml in lean rats [LR] (34% of all lipop roteins) and 8.2 +/- 0.9 mg/ml in the obese rats [OR] (66% of all lipoprote ins). Lipid percentage composition of lipoproteins was similar in both grou ps. The particle size of LDL and HDL was much higher in OR than in LR: LDLs weighed 31.1 +/- 7.5 ag (LR) vs. 273 +/- 81 ag (OR), and HDLs weighed 31.7 +/- 12.6 ag (LR) and 375 +/- 103 ag (OR). In chylomicra and VLDL there was a relative scarcity of apoproteins in OR compared with LR. The whole archi tecture of LDLs is altered in OR, with a predominance of surface lipids: ph ospholipid and free cholesterol, and lower amounts of core lipids: triacylg lycerols and cholesterol esters, with surface/core lipids ratios of 0.74 (L R) and 1.89 (OR). The consequences of anomalous LDL and HDL composition, si ze and overall structure may result in magnified lipoprotein metabolism alt erations that hamper their ability to transfer apolipoproteins to larger ch ylomicra. and VLDL, and to alter cholesterol transfer and binding of their apoproteins to cell surface receptors. The smaller number of LDL and HDL pa rticles may further compound these difficulties and thus change the free to esterified cholesterol ratios observed in OR. Conclusions: The main conclusions of this study are the key importance of c hylomicron analysis for a better understanding of the transfer of lipids, a nd the altered lipoprotein size and apoprotein distribution in obese rats, which seriously hamper cholesterol interchange, resulting in hypercholester olaemia, and thus triggering even more far-reaching consequences for the we llbeing of the obese.