Multicompartmental analysis of the effects of dietary fat saturation and cholesterol on absorptive lipoprotein metabolism in the rat

The potential contribution of the metabolism of absorptive lipoproteins to effects of dietary cholesterol and saturated (versus polyunsaturated) fat on plasma lipids and lipoproteins was studied in rats. Recipients were fed either a commercial stock diet, a low fat/cholesterol-free semipurified diet with a neutral P/S ratio, or one of two high fat/cholesterol-containing diets that had a high (4.6) or low (0.2) P/S ratio. Chylomicrons and intestinal very low-density lipoproteins labeled with ³H-oleic acid and/or ¹⁴C-cholesterol were isolated from donor rats receiving the high or low P/S ratio oil and were injected into recipients. Data on plasma disappearance and hepatic recovery of labels were analyzed by compartmental analysis. A multicompartmental model was required to fit these data and included steps interpreted to correspond to activation of newly secreted intestinal lipoproteins; delipidation on capillary endothelia by lipoprotein lipase, with transfer of cholesterol to other lipoproteins and tissue uptake of cholesterol and fatty acids; hepatic clearance of remnants; and secretion of lipoproteins by the liver. Metabolic state of the recipients (especially plasma triglyceride concentrations) had a greater influence on the rate of chylomicron turnover than did the source of donor chylomicrons, although saturated chylomicrons tended to be metabolized more slowly than polyunsaturated ones. For recipients fed the commercial stock diet and injected with saturated (versus polyunsaturated) chylomicrons, the mechanistic model predicted an increased retention of triglycerides during remnant formation, and thus an increased delivery of triglyceride to the liver. A consequent elevation in hepatic production of very low-density lipoprotein triglycerides may be related to the observed slower clearance of chylomicrons and increased plasma lipid levels in rats fed saturated fat and cholesterol.