ORIGINAL ARTICLE Anomalous lipoproteins in obese Zucker rats M. Blay, J. Peinado-Onsurbe, J. Julve, V. Rodrõ Âguez, J. A. Ferna  ndez-Lo  pez, X. Remesar and M. Alemany Centre de Recerca en Nutricio  i Cie Áncia dels Aliments, Universitat de Barcelona, Barcelona, Spain Aims: Obesity is characterized by dislipoproteinaemia with increased cholesterol and triacylglycerol levels and lower chylomicra disposal rates. We studied 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 lipoprotein classes (chylomicra, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)) by differential centrifugation. The apoprotein and lipid composition of each fraction were measured. 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 lipids and protein in each fraction/ml of plasma allowed the estimation of mean particle concentration and then the number of molecules of lipid and protein/unit of lipoprotein micelle. Results: A large part of hyperlipidaemia of obese rats is due to the accumulation of chylomicra: 1.3 6 0.2 mg/ml in lean rats [LR] (34% of all lipoproteins) and 8.2 6 0.9 mg/ml in the obese rats [OR] (66% of all lipoproteins). Lipid percentage composition of lipoproteins was similar in both groups. The particle size of LDL and HDL was much higher in OR than in LR: LDLs weighed 31.1 6 7.5 ag (LR) vs. 273 6 81 ag (OR), and HDLs weighed 31.7 6 12.6 ag (LR) and 375 6 103 ag (OR). In chylomicra and VLDL there was a relative scarcity of apoproteins in OR compared with LR. The whole architecture of LDLs is altered in OR, with a predominance of surface lipids: phospholipid and free cholesterol, and lower amounts of core lipids: triacylglycerols and cholesterol esters, with surface/core lipids ratios of 0.74 (LR) and 1.89 (OR). The consequences of anomalous LDL and HDL composition, size and overall structure may result in magni®ed lipoprotein metabolism alterations that hamper their ability to transfer apolipoproteins to larger chylomicra and VLDL, and to alter cholesterol transfer and binding of their apoproteins to cell surface receptors. The smaller number of LDL and HDL particles may further compound these dif®culties and thus change the free to esteri®ed cholesterol ratios observed in OR. Conclusions: The main conclusions of this study are the key importance of chylomicron analysis for a better understanding of the transfer of lipids, and the altered lipoprotein size and apoprotein distribution in obese rats, which seriously hamper cholesterol interchange, resulting in hypercholesterolaemia, and thus triggering even more far-reaching consequences for the well- being of the obese. Keywords: lipoproteins; obesity; apoproteins; Zucker fa/fa; chylomicra; very low density lipoprotein, low density lipoprotein, high density lipoprotein Received 24 April 2000; returned for revision 25 May 2000; revised version accepted 26 June 2000 Correspondence: Professor Dr Maria Á Alemany, Centre de Recerca en Nutricio  i Cie Áncia dels Aliments, Departament de BioquõÂmica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028 Barcelona, Spain. E-mail: alemany@bio.ub.es | OA ã 2001 Blackwell Science Ltd Diabetes, Obesity and Metabolism, 3, 2001, 259±270 | 259