Dietary fat saturation distinctly affects apolipoprotein gene expression and high density lipoprotein size distribution in two strains of Golden Syrian hamsters
Introduction
Dietary fat and cholesterol influence plasma lipoprotein levels and, therefore, play a significant role in the development of atherosclerosis and cardiovascular disease. However, the plasma lipid response to dietary modifications displays a considerable inter-individual variability as demonstrated in both humans and animal models. There is increasing evidence suggesting that genetic factors determine an important fraction of this individual variability [1].
Several dozens of candidate genes involved in lipoprotein metabolism have been characterized and polymorphisms at these loci have been useful in assessing the contribution of some of these genes to plasma lipid levels, dietary response and cardiovascular risk in humans [1]. These observations have been tested at a more mechanistic level using several animal models. Most of the initial research to identify genetic factors influencing responsiveness to dietary fat and cholesterol was carried out in mice due to the extensive genetic characterization of this species and the economical advantages. Non-human primates have also been studied in terms of genetic variability affecting dietary response. Although these species are genetically very close to humans, their availability and expense limit their usefulness. More recently, the hamster has become a widely used animal model for the study of human lipid metabolism. Several reports have demonstrated the similarities in lipoprotein metabolism between hamsters and humans. Thus, circulating levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol in hamsters more closely resemble those seen in humans than in other rodents [2], while receptor-dependent and independent LDL uptake is qualitatively similar to humans, although quantitatively more pronounced [3]. Moreover, hamsters respond to atherogenic diets by developing foam cells and atherosclerotic lesions similar to those seen in humans [4].
HDL particles are heterogeneous as result of variations in their lipid and protein constituents. HDL2 is a larger and less dense particle containing more core lipids and less protein than HDL3. It has become apparent that HDL2 and HDL3 are further separable based on particle size into several subfractions; HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c [5]. Some studies have shown that the inverse relation between plasma HDL concentrations and the risk of coronary heart disease [6] is primarily due to the HDL2b fraction, whereas HDL3 concentrations may not have a significant predictive value [7]. The distribution of lipids in HDL subclasses is an important determinant of HDL levels. HDL particle distribution is affected by lecithin: cholesterol acyltransferase (LCAT, EC 2.3.1.43), cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL, EC 3.1.1.34) and hepatic lipase (HL, EC 3.1.1.3). In addition, the apoA-I/apoA-II ratio may modulate the HDL particle distribution [8].
The influence of fat saturation on HDL metabolism has been examined in several models [9], [10], [11], [12]. A frequent finding is that polyunsaturated fat results in lower HDL cholesterol (HDL-C). This result is paradoxical because a diet rich in polyunsaturated fat has been shown to induce less severe atherosclerosis than a diet rich in saturated fat, even though the former diet results in lower HDL-C concentrations. We have previously reported that dietary fat saturation affects HDL metabolism in F1B hamsters, a hybrid strain known for its dietary hyper-responsiveness [13]. In the present study we have analyzed the differential response on plasma lipids, hepatic and intestinal gene expression and HDL subclass distribution in two hamster strains with different diet responsiveness, the F1B and the LVG. Our data demonstrate that HDL size distribution in hamsters is affected by dietary fat saturation and strain. Moreover, the expressions of apoA-II, C-II, and C-III gene are associated with the regulation of HDL particle size distribution.
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Animals
Twenty-four F1B (Biobreeders, Fitchburg, MA) and 24 LVG (Charles River Breeding Laboratory, Wilmington, MA) male hamsters (13 week old) were individually housed in stainless steel suspended rodent cages with free access to Purina 5001 rodent meal (Purina Mills, St.Louis, MO) and water. Animals were acclimated for 2 weeks and all were exposed to same room environmental factors so previous and experimental condition effects were minimal. The animals were maintained in American Association for the
Body weight and liver weight
At the end of the experimental period, F1B animals had a significantly lower weight (P < 0.01) than LVG animals while consuming a saturated-rich fat diet (146 ± 14 g and 175 ± 20 g, respectively) or a polyunsaturated-rich fat diet (137 ± 13 g and 199 ± 35 g, respectively). Dietary fat saturation did not have a significant effect on their body weight. A similar effect was noted in regard to liver weight, and no differences in the body to liver weight ratio for any group of animals (data not
Discussion
Plasma lipids, HDL particle size distribution and apolipoprotein gene expression were compared in the two strains of hamsters consuming different dietary fats. Several important differences in lipid metabolism were demonstrated between LVG and F1B animals. First, plasma lipoprotein profile in LVG hamsters was less atherogenic compared with F1B hamsters regardless of the dietary intervention. Second, the effect of dietary fat saturation on HDL particle distribution were different between the two
Acknowledgements
Supported by NIH grant HL54776 from the National Institutes of Health and contract 53–3K06–5-10 from the USDA Department of Agriculture Research Service. J.P-B was supported by a fellowship from the Spanish Ministry of Health (FIS 5499/96).
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