Marc S. Lambert

Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants

Possible changes in the fatty acid composition of dietary fats and oils which might occur during digestion, absorption and formation of chylomicrons and chylomicron remnants were investigated. Chylomicrons were collected from the thoracic duct of rats tube-fed with olive, maize, palm or fish oil or butter fat, and their fatty acid composition was determined and compared with that of their parent lipids. In turn, these lipoproteins were converted to chylomicron remnants in functionally hepatectomized rats and their composition re-determined. The predominant fatty acids in each of the oils and fats also predominated in their respective chylomicrons, but their proportions were reduced during the processes leading to their formation. Endogenous contributions of linoleic, eicosapentaenoic, and docosahexaenoic acids were particularly noted when these fatty acids were not well-represented in the original oils and fats, suggesting that they may be obligatory constituents in the formation of chylomicrons. The conversion of chylomicrons to remnants further attenuated the extremes in fatty acid composition of the dietary oils and fats. These results indicate that following an acute intake of oil or fat, the resulting chylomicrons and chylomicron remnants presented to the tissues contain a more balanced distribution of saturated, mono- and polyunsaturated fatty acids than the oils and fats from which they were derived.

Comparison of the hepatic uptake and processing of cholesterol from chylomicrons of different fatty acid composition in the rat in vivo

The effect of the fatty acid composition of chylomicrons on the uptake and processing of the cholesterol they carry was investigated in the rat in vivo. Rats kept on a standard low fat pellet diet and tube fed a single dose of palm, olive, corn or fish oil (rich in saturated, n-9 monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids, respectively) were used to prepare [3H]cholesterol-labelled chylomicrons of different fatty acid composition. These were then injected intravenously into rats (kept on the standard diet), and the clearance of radioactivity from the blood, distribution in the plasma lipoprotein density fractions, uptake by the liver and appearance in the bile were studied. [3H]Cholesterol from fish and corn oil chylomicrons was cleared from the blood more rapidly than that from palm and olive oil chylomicrons. After 180 min the proportion of the radioactivity present in the plasma in high density lipoprotein (HDL) was less when the chylomicrons were derived from palm oil as compared to any of the other oils. Approx. 40% of the administered label was recovered in the liver after 180 min in all experiments. The percentage of the injected radioactivity secreted into bile during 180 min was significantly higher with corn and fish oil chylomicrons than with palm oil chylomicrons, with chylomicrons from olive oil in an intermediate position, and these differences were most pronounced between 60 and 120 min after administration of the label. These studies clearly demonstrate that the fatty acid composition of chylomicrons has important effects on the hepatic uptake and processing of the cholesterol they carry, with enrichment with polyunsaturated fatty acids leading to an increased rate of uptake and more rapid removal from the body via the bile as compared to enrichment with saturated or monounsaturated fatty acids.

Comparison of short- and long-term effects of different dietary fats on the hepatic uptake and metabolism of chylomicron remnants in rats

The uptake and metabolism of [14C]oleate-labelled chylomicron remnants derived from olive oil, maize oil, palm oil, fish oil or butter fat was investigated using perfused livers from rats fed on the corresponding fat-supplemented diet (providing 40% of the dietary energy) or a low-fat diet for 21 d. The percentage of added [14C]oleate-labelled remnant removed from the perfusate was similar for livers from rats fed on the fat-supplemented diets irrespective of the type of fat fed, whereas livers from rats fed on the low-fat diet removed more labelled fish oil and butter fat remnants than olive, maize or palm oil remnants. Following hepatic uptake in the fat-supplemented groups, the oxidation of [14C]oleate-labelled remnant lipid from maize oil, fish oil, and butter fat remnants was greater than that of the lipids from olive and palm oil remnants, although only the oxidation of lipids from maize and palm oil remnants was increased by prior fat-supplementation of the diet. In addition, the livers from rats fed on the fish-oil-supplemented diet incorporated more [14C]oleate-labelled remnant lipid into phospholipid compared with the livers from rats fed on the other fat-supplemented diets or the low-fat diets. These investigations show that both prior fat feeding and the composition of the fat fed, as well as the fatty acid composition of the chylomicron remnant particles themselves, influence the uptake and metabolism of chylomicron remnants by the liver.

The differential hepatic uptake of chylomicron remnants of different fatty acid composition is not mediated by hepatic lipase

The hypothesis that hepatic lipase mediates the differential hepatic uptake of chylomicron remnants of different fatty acid composition, demonstrated in previous work from our laboratory, was tested by investigating the effect of antibodies to the enzyme on the uptake of remnants enriched with saturated or n-3 polyunsaturated fatty acids by the perfused rat liver. After perfusion of rat livers with polyclonal antibodies to rat hepatic lipase raised in rabbits or with rabbit non-immune serum for 15 min, [3H]oleate-labelled chylomicron remnants, derived from chylomicrons of rats given a bolus of either palm (rich in saturated fatty acids) oil or fish (rich in n-3 polyunsaturated fatty acids) oil, were added. The disappearance of radioactivity from the perfusate during 120 min and its recovery in the liver at the end of the experiments were then measured. Although the rabbit anti-rat hepatic lipase antiserum was shown to inhibit hepatic lipase activity by up to 90%, and to bind extensively to hepatic sinusoidal surfaces when added to the perfusate, radioactivity from remnants of chylomicrons from rats given a bolus of fish oil as compared with palm oil disappeared from the perfusate and appeared in the liver more rapidly in the presence both the antiserum and the non-immune serum, and the differences between the uptake of the two types of remnants were similar. We conclude, therefore, that differential interaction with hepatic lipase is not responsible for the differences in the rate of removal of chylomicron remnants of different fatty acid composition from the blood.

The type of dietary fat alters the hepatic uptake and biliary excretion of cholesterol from chylomicron remnants.

The consumption of fat-enriched diets may alter the uptake and metabolism of chylomicron remnant cholesterol by the liver. To test this hypothesis, [3H]cholesterol-labelled chylomicron remnants derived from different dietary fats were studied in perfused livers both from rats fed on diets enriched in the corresponding fats and from rats fed on a low-fat diet. Livers from rats fed on each of the fat-enriched diets removed similar amounts (34-40%) of the [3H]cholesterol-labelled remnants added, whereas livers from rats fed on the low-fat diet removed significantly more labelled fish-oil and butter-fat remnants than olive-, maize- or palm-oil remnants. Significantly more remnant [3H]cholesterol was secreted into the perfusate HDL by livers from rats fed on the olive-oil, fish-oil and butter-fat diets when compared with those from rats fed on the low-fat diet or the maize-oil diet. Furthermore, the excretion of remnant [3H]cholesterol via the bile acid was increased by the olive-, maize-, palm- or fish-oil diets, and decreased by the butter-fat diet when compared with the low-fat diet, although the [3H]bile acid excreted remained less on saturated fat diets. This investigation shows that the hepatic uptake and subsequent metabolism of cholesterol from chylomicron remnants is influenced by the type of fat in the diet as well as the fatty acid composition of the particles themselves, and may help to explain some of the hyper- and hypocholesterolaemic effects of saturated and unsaturated fatty acids.