The effect of chronic cholesterol feeding on intestinal lipoproteins in the rat

Abstract

Chronic cholesterol feeding has been shown to produce abnormal plasma lipoproteins in a variety of experimental animals and man. In order to explore the role of the intestine in the production of these abnormal lipoproteins, rats were chronically fed a diet containing 1% cholesterol and 10% olive oil and were compared to control animals, fed either normal chow or normal chow containing 10% olive oil. Mesenteric lymph lipoproteins from fasting lymph and from lymph obtained after acutely infusing cholesterol and olive oil were examined and compared to plasma lipoproteins from these animals. There were no differences in apoA-I output, cholesterol output, or distribution in lymph lipoproteins between the two groups of controls. The cholesterol-olive oil diet produced a mild hyperlipidemia (plasma cholesterol 81 –> 95 mg/dl, plasma triglyceride 95 –> 162 mg/dl). Plasma lipoprotein electrophoresis revealed an abnormal band with broad beta mobility and a reduction in HDL. Lipid analysis of ultracentrifugally separated fractions demonstrated the appearance of an intermediate density (1.006-1.030 g/ml) lipoprotein in plasma markedly enriched in cholesteryl esters. Analysis of fasting mesenteric lymph from chronically cholesterol-fed animals revealed similar apoA-I, cholesterol, and triglyceride outputs when compared to controls. Although in both groups most of the cholesterol was transported in d 1.006 g/ml lipoproteins. In the chronically cholesterol-fed animals, 19% of fasting lymph cholesterol was transported in a lipoprotein of density 1.006-1.030 g/ml, compared to 4% in this density in controls. During the acute infusion of cholesterol and olive oil, the output of lymph apoA-I (226 +/- 20 versus 374 +/- 5 micro g/hr, P < 0.025) and lymph cholesterol (970 +/- 82 +/- 1774 micro g/hr, P < 0.01) was significantly lower in the chronically cholesterol-fed group, despite no significant change in triglyceride outputs (49 +/- 2 versus 58 +/- 7 mg/hr). Analysis of individual lymph lipoproteins from chronically cholesterol-fed animals revealed that significantly less apoA-I and cholesterol was carried in d < 1.006 g/ml lipoproteins than in controls. There was however, both a relative and absolute increase in the cholesterol and apoA-I content of intermediate and low density lymph subfractions. Particularly prominent in lymph from chronically cholesterol-fed animals was a lipoprotein (d 1.006-1.030 g/ml) which was inconsistently found in controls. This particle was rich in cholesterol and contained apoA-I. [(3)H]Retinol infusion studies revealed that this particle contained increased retinyl ester when compared to plasma, suggesting an intestinal origin. These results demonstrate that chronic cholesterol feeding in the rat results in altered mesenteric lymph lipoproteins which may contribute to the abnormalities found in plasma.-Riley, J. W., R. M. Glickman, P. H. R. Green, and A. R. Tall. The effect of chronic cholesterol feeding on intestinal lipoproteins in the rat.