Action of liproprotein lipase on apoprotein-depleted chylomicrons.

1. Rat lymph chylomicrons were exposed to soluble and to immobilized trypsin. This treatment caused no detectable changes in the chylomicron structure or lipid composition, but did result in virtually total depletion of all their tetramethylurea-soluble apoproteins. 2. The capacity of these apoprotein-depleted chylomicrons to act as substrate for lipoprotein lipase in vitro and in situ (i.e. isolated perfused rat heart) was decreased by about 90 and 75% respectively, compared with intact chylomicrons. 3. On incubation with rat plasma high-density lipoproteins, trypsin-treated chylomicrons readily acquired a full apoprotein complement. This resulted in the complete restoration of their capacity to act as substrate for lipoprotein lipase both in vitro and in situ. 4. It is suggested that with the use of try,sin-treated chylomicrons it is now possible for the first time to investigate the physiological role that individual apoproteins play in the catabolism of triacylglycerol-rich lipoproteins by lipoprotein lipase.     

Lipoprotein metabolism in the suckling rat: characterization of plasma and lymphatic lipoproteins

Suckling rat plasma contains (in mg/dl): chylomicrons (85 +/- 12); VLDL (50 +/- 6); LDL (200 +/- 23); HDL1 (125 +/- 20); and HDL2 (220 +/- 10), while lymph contains (in mg/dl): chylomicrons (9650 +/- 850) and VLDL (4570 +/- 435) and smaller amounts of LDL and HDL. The lipid composition of plasma and lymph lipoproteins are similar to those reported for adults, except that LDL and HDL1 have a somewhat higher lipid content. The apoprotein compositions of plasma lipoproteins are similar to those of adult lipoproteins except for the LDL fraction, which contains appreciable quantities of apoproteins other than apoB. Although the LDL fraction was homogeneous by analytical ultracentrifugation and electrophoresis, the apoprotein composition suggests the presence of another class of lipoproteins, perhaps a lipid-rich HDL1. The lipoproteins of lymph showed low levels of apoproteins E and C. The triacylglycerols in chylomicrons and VLDL of both lymph and plasma are rich in medium-chain-length fatty acids, whereas those in LDL and HDL have little or none. Phospholipids in all lipoproteins lack medium-chain-length fatty acids. The cholesteryl esters of the high density lipoproteins are enriched in arachidonic acid, whereas those in chylomicrons, VLDL, and LDL are enriched in linoleic acid, suggesting little or no exchange of cholesteryl esters between these classes of lipoproteins. The fatty acid composition of phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine were relatively constant in all lipoprotein fractions, suggesting ready exchange of these phospholipids. However, the fatty acid composition of phosphatidylethanolamine in plasma chylomicrons and VLDL differed from that in plasma LDL, HDL1, and HDL2. LDL, HDL1, and HDL2 were characterized by analytical ultracentrifugation and shown to have properties similar to that reported for adult lipoproteins. The much higher concentration of triacylglycerol-rich lipoproteins in lymph, compared to plasma, suggests rapid clearance of these lipoproteins from the circulation.     

The lecithin-cholesterol acyl transferase activity of rat intestinal lymph.

The lecithin-cholesterol acyl transferase (LCAT) activity in rat mesenteric lymph was examined as a possible source of chylomicron cholesteryl ester. Lymph activity was only 2-3% of rat serum activity. Removal of d less than 1.006 lipoproteins increased lymph LCAT activity, but only to 6-8% of that of serum. Relative to total cholesterol in the d greater than 1.08 g/ml fractions, lymph LCAT activity in lymph from fasting rats was less than serum, but in lymph from nonfasting rats the ratio LCAT/HDL-cholesterol reached levels greater than serum, suggesting a contribution of enzyme from the gut. Both LCAT activity and HDL concentration in mesenteric lymph increased during feeding. Subfractions of lymph that inhibited serum LCAT were: chylomicrons, VLDL, chylomicron lipid, VLDL apoprotein, and HDL apoprotein. In the rat, the low LCAT activity of mesenteric lymph was in part due to the low enzyme concentration present, and the activity was apparently lowered further by lipid-rich lipoproteins that inhibited the reaction. Enzyme inhibition due to the apoprotein fractions of lipoproteins is probably minor in the rat in vivo.     

Characteristics of chylomicron binding and lipid uptake by endothelial cells in culture.

Bovine vascular endothelial cells bind chylomicrons via a high affinity membrane receptor site. Subsequent to binding, the chylomicron apoprotein was neither internalized nor degraded by either sparse or confluent (contact-inhibited) cells. However, the adsorption of chylomicrons was associated with interiorization of chylomicron cholesteryl ester and triglyceride and the hydrolysis of these lipids to free cholesterol and unesterified fatty acids by a lysosome-dependent pathway. This pathway was active in both subconfluent and contact-inhibited cells. The chylomicron free cholesterol so produced inhibited endogeneous cholesterol synthesis measured in terms of the incorporation of [1-14C]-acetate into sterol. An excess of high density lipoprotein was 2- to 3-fold more effective in reducing both binding of chylomicrons and interiorization of chylomicron lipid than was low density lipoprotein. Chylomicron binding was not "down-regulated" by preincubation of the cells with low density lipoprotein or chylomicrons. The results are discussed in the context of cholesterol sources for contact-inhibited endothelial cells which do not interiorize low density lipoprotein cholesterol.     

Apolipoprotein A-IV: a protein occurring in human mesenteric lymph chylomicrons and free in plasma. Isolation and quantification.

1. Human mesenteric lymph chylomicrons were isolated from chylous ascites fluid by ultra-centrifugation and agarose/gel chromatography and their apoprotein composition was analysed by dodecylsulfate/polyacrylamide gel electrophoresis, analytical isoelectric focusing and immuno-chemically. Major components of mesenteric lymph chylomicrons were apoprotein A-I, proteins of Mr less than 15 000 including the C-group apoproteins and a protein of Mr 46 000. Minor components were apoprotein E and a protein of Mr approximately equal to 200 000 (B-like protein). This apoprotein composition was qualitatively identical with that of chylomicrons from intestinal lymph of the rat, but was distinctly different from plasma chylomicrons of humans with fasting chylomicronaemia. 2. The protein of Mr approximately equal to 46 000 has been isolated by preparative dodecylsulfate/polyacrylamide gel electrophoresis from human and rat lymph chylomicrons and was compared to a protein of identical Mr present in rat high-density lipoproteins (apoplipoprotein A-IV) and in the rho less than 1.006 g/ml serum lipoprotein fraction of individual humans with alimentary hypertriglyceridaemia. In both species the 46 000-Mr proteins isolated from lymph and serum were identical according to amino acid composition and isoelectric point in 6 M urea. The human proteins from both sources were also immunologically identical. The similarities in the molecular properties of the human apolipoprotein and rat apolipoprotein A-IV indicate that these proteins are homologous. 3. Plasma levels of human apolipoprotein A-IV determined by electroimmunodiffusion were 14.15 +/- 3.66 mg/100 ml (n = 59), but greater than 90% of the protein was unassociated with the major lipoprotein fractions. It is concluded, that apolipoprotein A-IV is a main protein component of human lymph chylomicrons, that is removed from the particles in the plasma compartment.     

Physical and chemical changes in isolated chylomicrons: prevention by EDTA

When washed chylomicrons obtained from the lymph of rats, which had been fed corn oil, were maintained at 0-4 degrees C in 0.9% NaCl, the following physical and chemical changes were observed to occur: increased polarity of chylomicron lipids, increased ultraviolet absorption of chylomicron lipids at 232 nm, decreased linoleic acid content, and aggregation. These alterations occurred more rapidly at room temperature and were found to be associated with an increased lipid peroxide content. The behavior of isolated olive oil chylomicrons was qualitatively similar. All observed changes in the properties of washed chylomicrons were prevented by 0.25 mm EDTA; when tested, 25 micro m EDTA was equally effective. The changes were also prevented by 0.02% hydroquinone. The alterations in chylomicron lipids appear to result from the autoxidation of esterified linoleic acid. Studies with linoleic acid-U-(14)C-labeled chylomicrons indicated that cleavage of the linoleic acid carbon chain did not accompany the physicochemical changes. These results demonstrate the usefulness of EDTA in preventing these specific and progressive alterations in chylomicrons dispersed in aqueous systems.     

A new method for the study of chylomicron kinetics in vivo

Our understanding of the metabolism of chylomicrons, the lipoprotein that transports dietary fat from the intestine to peripheral tissues, is incomplete. The present studies were conducted to determine whether a labeled intravenous lipid emulsion could be used to estimate chylomicron triglyceride (TG) rate of appearance (R(a)) and thereby quantify the rate of intestinal fat absorption. After an overnight fast, healthy volunteers (n = 6) sipped a (3)H-labeled drink over 6.5 h at a rate of 175 mg fat. kg(-1). h(-1). Beginning at hour 5, an HPLC-purified, (14)C-labeled lipid emulsion was infused intravenously for 90 min. During the study, plasma total and chylomicron TG concentrations increased from 100 +/- 21 to 237 +/- 40 mg/dl and from undetectable to steady-state levels of 35 +/- 13 mg/dl, respectively. After a minor correction for VLDL contamination, tracer-determined chylomicron TG R(a) was 175 +/- 30 mg. kg(-1). h(-1), equal to the presumed ingestion rate. In summary, a radiolabeled intravenous lipid emulsion is able to accurately estimate chylomicron TG R(a) and therefore can be used to measure in vivo fat absorption rates.     

The effects of Triton WR-1339, protamine sulfate and heparin on the plasma removal of emulsion models of chylomicrons and remnants in rats

Protein-free lipid emulsions with compositions modelling chylomicrons (chylomicron-like emulsion) or chylomicron remnants (remnant-like emulsion) were injected intra-arterially into nonanesthetized rats. Compared with control untreated rats, treatment with Triton WR-1339, protamine sulfate or heparin strongly modified the plasma removal of triacylglycerols and cholesteryl ester moieties of chylomicron-like emulsions, but had little effect on removal rates of triacylglycerols or cholesteryl esters of remnant-like emulsions. The effects on chylomicron-like removal were similar to those on natural lymph chylomicrons. The relative lack of effects on remnant-like emulsion removal provides additional evidence that remnant-like emulsions are a metabolic model for natural chylomicron remnants.     

Retention of lipolytic products in chylomicrons incubated with lipoprotein lipase: electron microscope study.

Early effects of lipolysis on the structure of chylomicrons in vitro were studied in rat chylomicrons incubated with purified bovine mild lipoprotein lipase at pH 8.1. The amount of the albumin added to the incubation medium was limited so that free fatty acids (FFA) and partial glycerides formed during lipolysis would accumulate in the chylomicrons. The structures visualized in lipolyzed chylomicrons was found to be affected by pH during preparation of specimens for microscopy, whether fixed with OsO4 and sectioned, or stained with sodium phosphotungstate and examined as whole mounts. Circular aqueous spaces were present in the triglyceride core of lipolyzed chylomicrons processed at pH 8.1 and 7.4. Sometimes the spaces contained aggregates of osmiophilic material and whorls of bilayered lamellae. The spaces were replaced by lamellar structures having a periodicity of 40 A, in chylomicrons processed at pH 5.5, and the spaces and lamellae were both absent at pH 3.0. The findings indicate that these spaces were lined by a lipid monolayer which formed bilayered lamellae under certain conditions. It is concluded that the monolayer lining the aqueous spaces is an inward extension of the chylomicron surface film produced by the accumulation and movement of lipolytic products, FFA and partial glycerides, in the interfacial plane between core triglyceride and water.     

Comparison of the metabolic effects of chylomicrons and their remnants on isolated hepatocytes

A comparison was made between the effects of chylomicrons and chylomicron remnants on metabolic processes of isolated hepatocytes. Since isolated triacylglycerol-rich lipoproteins are contaminated with nonesterified fatty acids, control incubations were conducted with an amount of fatty acid equivalent to the contaminating fatty acids present in the chylomicrons and the remnant preparations, respectively. Chylomicron remnants, produced in vitro by incubation of chylomicrons in postheparin rat plasma, caused marked inhibition of glycolysis, fatty acid synthesis, and cholesterol synthesis, along with marked stimulation of ketogenesis. These effects were traced to the release of nonesterified fatty acids from these remnant particles as a consequence of contamination with lipoprotein lipase, picked up by the particles during the incubation with rat plasma. Fatty acids inhibit glycolysis, cholesterol, and fatty acid synthesis, but enhance ketone body formation by isolated hepatocytes. Chylomicrons and remnants prepared in vivo by the injection of chylomicrons into functionally hepatectomized rats were not contaminated with lipoprotein lipase and did not inhibit glycolysis and cholesterol synthesis nor increase ketone body formation. These lipoprotein particles did, however, cause significant inhibition of fatty acid synthesis, with the chylomicrons being more effective on a protein basis than the remnants produced in vivo. The mechanism responsible for the inhibition of fatty acid synthesis by chylomicrons and remnants prepared in vivo remains to be resolved.     

Origin and transport of the A-I and arginine-rich apolipoproteins in mesenteric lymph of rats.

Transport of apolipoprotein A-I and argininerich apolipoprotein in mesenteric lymph was examined in rats given constant intraduodenal infusions of saline, glucose in saline, or emulsified fat. Lymph flow in all groups was constant from 5 to 50 hr after beginning the infusions. Lymphatic transport of triglycerides was about 20-fold greater and transport of apoprotein A-I was about twofold greater in fat-infused rats than in the other two groups. In each group transport of apoprotein A-I bore a significant positive relationship to transport of triglycerides. Lymphatic transport of the arginine-rich apoprotein was only 6-12% of that of apoprotein A-I and was more closely related to lymphatic transport of total protein than to that of triglycerides. In fat-infused rats given [(3)H]lysine intraduodenally, about two-thirds of the (3)H in the chylomicron proteins was in apoprotein A-I and only about 1% was in the arginine-rich apoprotein. Estimated specific activity of chylomicron proteins was highest for apoprotein A-I and apoprotein A-IV, and lowest for the arginine-rich apoprotein and proteins of low molecular weight (mainly C apoproteins). In fat-infused rats given constant intravenous infusions of radioiodinated high density lipoproteins from blood plasma, the specific activity of apoprotein A-I in lymph chylomicrons was only about 5% of that of apoprotein A-I in blood high density lipoproteins, indicating that more than 90% of the apoprotein A-I in chylomicrons was synthesized in the intestine. From these and other data it is concluded that both the intestine and liver are significant sources of apoprotein A-I whereas only the liver synthesizes significant amounts of the arginine-rich apoprotein.     

In vitro transfer of chylomicron retinol and retinyl esters

The redistribution of rat chylomicron retinoids following incubation with fasting- or postheparin human plasma was investigated. With fasting plasma, chylomicron retinol appeared among higher density lipoprotein acceptors and density greater than 1.21 gm/ml plasma proteins; only small amounts of retinyl ester were found therein. With postheparin plasma, retinyl ester-containing chylomicron remnants with densities spanning the low- and high density lipoprotein distributions were generated; appreciable quantities of retinyl esters appeared among rho greater than 1.019 lipoproteins only in the presence of postheparin plasma. These observations are consistent with the conservation of retinyl esters, but not retinol, among chylomicrons and their catabolic products.     

Uptake of chylomicron remnants by the liver: further evidence for the modulating role of phospholipids

Rat lymph chylomicrons were treated with rat heparin-releasable hepatic lipase (HL) or with bovine milk lipoprotein lipase (LPL). The ability of the resulting particles to be taken up by the liver in vivo was assessed following their infusion into the portal vein of partially hepatectomized animals. The following observations were made: a) the rate of phospholipid depletion, relative to the rate of triglyceride hydrolysis, induced by HL was two- to threefold higher than that observed for LPL; b) the depletion of at least 57% of phospholipids from the surface of HL-treated chylomicrons caused no major alterations in the apoprotein profile of the particles; c) for the same extent of triglyceride hydrolysis, HL-treated chylomicrons were taken up by liver at a rate significantly higher (P less than 0.005) than LPL-treated particles; d) the liver uptake of HL-treated chylomicrons was competitively inhibited by endogenously generated chylomicron remnants, indicating that these two types of lipoproteins share the same process of recognition and uptake by liver cells. It is concluded that the in vivo changes in phospholipid content, or composition, on the surface of chylomicrons during their transformation into remnants, modulate the differentiation of these two particles by the hepatic remnant receptor.     

Effects of palm oil and transesterified palm oil on chylomicron and VLDL triacylglycerol structures and postprandial lipid response

The effects of positional distribution of triacylglycerol (TAG) fatty acids to TAG structures in chylomicrons and VLDL, and to postprandial lipemia, were studied in 10 healthy premenopausal women using a 6-h oral fat load test and a randomized, double-blind cross-over design. Molecular level information of TAG regioisomerism was obtained with a tandem mass spectrometric method. The positional distribution of fatty acids in chylomicron TAGs was similar to the respective dietary fat; 79% of the analyzed regioisomers in palm oil and 84% of the analyzed regioisomers in transesterified oil were found in chylomicron TAGs 3 h after the oral fat loads. VLDL TAGs were equal after the two fat loads in all but one regioisomer. Similarities in the fatty acid compositions of chylomicron TAGs suggest that palmitic acid was absorbed equally from both test fats. The proportion of palmitoleic acid in the chylomicrons was increased. Fat with palmitic acid predominantly in the sn-1 and sn-3 positions caused a larger incremental area of total TAGs in plasma and reduced plasma insulin values at the beginning of the postprandial response (0-90 min) compared with fat with palmitic acid randomly distributed. The relationship between TAG molecular structures in dietary fats and in lipoproteins provides new means for understanding the effects of fatty acid positional distribution on human lipid metabolism.     

EFFECTS OF LIPOPROTEIN LIPASE ON THE STRUCTURE OF CHYLOMICRONS

Chylomicrons isolated from rat lymph were complexed with lipoprotein lipase of post-heparin plasma (chylomicrons-LPL) in order to study the effects of lipolysis on the structure of chylomicrons. Triglyceride in the chylomicron core was readily hydrolyzed to free fatty acids (FFA) and glycerol when chylomicrons-LPL were incubated at pH 8.3 in medium containing albumin. Although most of the FFA were immediately released to the medium, some were retained within chylomicrons when FFA-binding sites on albumin were not available. These observations suggest that albumin may have a specific role in the transfer of FFA across the chylomicron surface film. Chylomicrons-LPL assumed many different shapes as they were depleted of triglyceride by the lipolytic action of the enzyme, and total removal of core triglyceride resulted in empty sacks of surface film. The surface film was visualized in sections of OsO₄-fixed chylomicrons-LPL as a thin electron-opaque line, 25–30 Å wide, in areas where the underlying electron-opaque core had been replaced by zones of decreased electron opacity, and in folds of surface film extending outward from chylomicrons partially depleted of core lipid. The findings demonstrate that chylomicrons consist of a core of liquid triglyceride enveloped by a pliable and durable monolayer surface film, and that lipoprotein lipase reduces the triglyceride core without disrupting the surface film.     

Influence of the fatty acid composition of lipids in chylomicron remnants derived from fish or corn oil on the lipid profile of cultured rat hepatocytes

The aim of this work was to characterise the lipid and fatty acid composition of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (PUFA) and to investigate their influence on the fatty acid profiles of the lipids of rat hepatocytes cultured in monolayers. Chylomicrons were prepared from the lymph collected from the thoracic duct of rats given an oral dose of fish or corn oil (high in n-3 and n-6 PUFA, respectively), and remnants were prepared in vitro from such chylomicrons using rat plasma containing lipoprotein lipase. The fatty acids predominating in the oils abounded also in their respective chylomicrons and remnants, especially in triacylglycerols. Chylomicrons as well as remnants contained small amounts of phospholipids and long-chain PUFA that were minor in, or absent from, the dietary oils, evidently provided by the intestinal epithelium. The incubation of hepatocytes for 6 h, with either n-3 or n-6 PUFA-rich remnants (0.25-0.75 mM triacylglycerol) resulted in a dose-dependent increase in the amount of triacylglycerols and phospholipids in the cells, which was not affected further by increasing the incubation time to 19 h. Whereas hepatocyte triacylglycerols mostly incorporated the PUFA predominating in each remnant type, the fatty acid profile of cell phospholipids was virtually unchanged. In addition, irrespective of whether they were enriched in n-3 or n-6 PUFA, remnants promoted a relative decrease in the amount of cholesteryl esters, a minor hepatocyte lipid class poor in PUFA. The results demonstrate that the hepatocyte fatty acid profile is modulated in a lipid-class specific way by the amount and type of dietary PUFA delivered to cells in chylomicron remnants.     

Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons

The triglycerides in chylomicrons are hydrolyzed by lipoprotein lipase (LpL) along the luminal surface of the capillaries. However, the endothelial cell molecule that facilitates chylomicron processing by LpL has not yet been defined. Here, we show that glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of chylomicrons. Gpihbp1-deficient mice exhibit a striking accumulation of chylomicrons in the plasma, even on a low-fat diet, resulting in milky plasma and plasma triglyceride levels as high as 5000 mg/dl. Normally, Gpihbp1 is expressed highly in heart and adipose tissue, the same tissues that express high levels of LpL. In these tissues, GPIHBP1 is located on the luminal face of the capillary endothelium. Expression of GPIHBP1 in cultured cells confers the ability to bind both LpL and chylomicrons. These studies strongly suggest that GPIHBP1 is an important platform for the LpL-mediated processing of chylomicrons in capillaries.     

Receptor-dependent uptake of human chylomicron remnants by cultured skin fibroblasts

Human chylomicrons were isolated from plasma from a subject with familial hypertriglyceridemia and converted to chylomicron remnants by incubation with postheparin plasma. The interaction of these apolipoprotein E-containing, cholesterol-rich human chylomicron remnants with cultured skin fibroblasts was studied. Chylomicron remnants were internalized by skin fibroblasts as a unit, mainly via the low density lipoprotein (LDL)-receptor pathway, resulting in increased cell cholesterol content. After entering the fibroblast, chylomicron remnants stimulated cholesterol esterification, suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and down-regulated LDL receptor activity similar to the action of LDL. As a function of increasing lipolysis, remnant particles were progressively more effectively taken up by skin fibroblasts, despite a decrease in the apolipoprotein E content per lipoprotein particle. Remnant particles produced after hydrolysis of 70 to 80% of chylomicron triglyceride increased cell cholesterol content to an amount nearly identical to that observed with LDL when the two lipoproteins were incubated at an equal cholesterol concentration. However, when incubated on the basis of equal particle number, chylomicron remnants were 2 to 3 times more effective than LDL in delivering cholesterol to the cells. These results suggest that chylomicron remnants play a role in the regulation of postabsorptive cholesterol homeostasis in nonhepatic cells, and possibly in the pathogenesis of atherosclerosis.     

Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver

Like rat C apolipoproteins, each of the C apolipoproteins from human blood plasma (C-I, C-II, C-III-1, and C-III-2) bound to small chylomicrons from mesenteric lymph of estradiol-treated rats and inhibited their uptake by the isolated perfused rat liver. This inhibitory effect of the C apolipoproteins was independent of apolipoprotein E, which is present only in trace amounts in these chylomicrons. Addition of rat apolipoprotein E to small chylomicrons from mesenteric lymph of normal rats did not displace C apolipoproteins and had no effect on the uptake of these particles by the perfused liver, indicating that an increased ratio of E apolipoproteins to C apolipoproteins on chylomicron particles, unaccompanied by depletion of the latter, may not promote recognition by the chylomicron remnant receptor. The hepatic uptake of remnants of rat hepatic very low density lipoproteins (VLDL) and small chylomicrons, which had been produced in functionally eviscerated rats, was also inhibited by addition of C apolipoproteins. These observations are consistent with the hypothesis that the addition of all of the C apolipoproteins to newly secreted chylomicrons and VLDL inhibits premature uptake of these particles by the liver and that depletion of all of these apolipoproteins from remnant particles facilitates their hepatic uptake. Remnants of chylomicrons and VLDL incubated with rat C apolipoproteins efficiently took up C-III apolipoproteins, but not apolipoprotein C-II (the activator protein for lipoprotein lipase). Preferential loss of apolipoprotein C-II during remnant formation may regulate the termination of triglyceride hydrolysis prior to complete removal of triglycerides from chylomicrons and VLDL.     

Metabolism of chylomicrons by the isolated rat liver

Isolated livers perfused with washed corn oil chylomicrons labeled in vivo with palmitic acid-1-(14)C removed a large proportion of the chylomicrons. Slices from these livers oxidized chylomicron fatty acid esters to both carbon dioxide and acetoacetate. The liver slices also generated free fatty acids from chylomicron lipids and converted chylomicron triglycerides to phospholipids. Similar activities were observed in rat liver slices prepared shortly after the intravenous administration of chylomicrons to intact rats. The observed chylomicron uptake and lipid conversions were similar in livers from both fed and fasted rats. Fasting increased the oxidation of chylomicron fatty acid esters by livers labeled in vivo and by perfusion. In livers removed from intact rats given labeled chylomicrons, the triglyceride-(14)C to phospholipid-(14)C ratio was high, a finding unexpected if the liver had acquired this (14)C by removal of circulating fatty acids formed by extrahepatic lipolysis. These results demonstrate the ability of the liver to remove and utilize chylomicrons directly and suggest that direct removal accounts for a significant portion of the chylomicron fatty acids utilized by the liver of intact rats.