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M Avella

Publications and source records attributed to M Avella.

At least 19 recordsLinked to original sources
PubMed2005

The role of protein kinase C in regulating equine eosinophil adherence and superoxide production.

OBJECTIVE: To determine if protein kinase C (PKC) regulates equine eosinophil function. MATERIAL OR SUBJECTS: Blood eosinophils were obtained from healthy ponies. METHODS: IL-5- and histamine-induced adherence to serum-coated plastic was measured as the eosinophil peroxidase content of adherent cells and serum treated zymosan (STZ)-and IL-5-induced superoxide production by the reduction of cytochrome C. Eosinophil PKC activity was quantitated as the rate of transfer of (32)P from ATP to substrate. The effects of Ro31-8220 (isotype non-selective PKC inhibitor), Go6976 (conventional PKC inhibitor), and rottlerin (PKCdelta inhibitor) were determined by ANOVA and Bonferroni's or Dunnett's test. RESULTS: Ro31-8220 and Go6976 reduced superoxide production whereas only Go6976 inhibited adherence. Rottlerin inhibited histamine-induced adherence and increased STZ-induced superoxide production. Ro31-8220 and Go6976, but not rottlerin, inhibited PKC activity. CONCLUSIONS: PKC is involved in regulating equine eosinophil adherence and superoxide production. The role of PKCdelta appears to depend upon the stimulus used and response measured.

Analysis of Variance↗
PubMed2004

The fatty acid composition of chylomicron remnants influences their propensity to oxidate.

BACKGROUND AND AIM: Although the replacement of saturated with unsaturated dietary fat has been advocated as a means of reducing the risk of cardiovascular disease, diets high in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, thus contributing to the pathogenesis of atherosclerosis. As the susceptibility of individual fatty acids to oxidation directly depends on their degree of unsaturation, and the oxidative modification of lipoproteins may be an important determinant of atherogenesis, the aim of this study was to evaluate the susceptibility to auto-oxidation and copper-mediated oxidation of chylomicron remnants (CMRs) enriched in n-3 or n-6 PUFA. METHODS AND RESULTS: The remnants were prepared in vitro from chylomicrons obtained from rats given an oral dose of fish or corn oil, using rat plasma containing lipoprotein lipase. Their propensity to oxidate and the extent of the oxidation were estimated by measuring the formation of conjugated dienes and the detrimental products of lipid peroxidation. The results showed that: 1) the corn oil CMRs contained a relatively high proportion of n-6 PUFA (mainly linoleic acid), whereas the fish oil CMRs contained more n-3 PUFA, mainly eicosapentanoic and docosahexaenoic acids; 2) n-3-rich CMRs have a significantly lower propensity to oxidate than n-6-rich CMRs despite their 50% lower alpha-tocopherol content and 40% higher unsaturation index. CONCLUSION: Our data indicate that the precise allocation of n-3 PUFA within the lipid core of CMRs may play a pivotal role in lowering the susceptibility to oxidation of fish CMRs by overcoming the effects of unfavourable alpha-tocopherol concentration. Eating n-3 rather than n-6 PUFAs seems to make CMRs more resistant against free radical attack, which may contribute to attenuating their potential atherogenic properties.

Animals↗
PubMed2003

Neurohypophysial hormone regulation of Cl- secretion: physiological evidence for V1-type receptors in sea bass gill respiratory cells in culture.

Neurohypophysial hormone receptors were studied in primary cultures of sea bass (Dicentrarchus labrax) gill respiratory-like cells grown on permeable supports. This preparation was previously shown to provide a functional model for investigating the hormonal regulation of Cl- secretion. Under control conditions, the cultured monolayered epithelium had a short-circuit current (ISC) of 3.5+/-1.1 micro A x cm(-2). This current had previously been identified as an active Cl- secretion. The addition of increasing concentrations of the fish neurohypophysial hormones, arginine vasotocin (AVT) or isotocin (IT), elicited a concentration-dependent stimulation of the ISC. Maximal increases of 60.9+/-12.1% and 117.7+/-28.0% above the basal ISC value were obtained for 10(-7) M AVT and IT respectively. Half-maximal effects were obtained for 3.1 x 10(-9) M AVT and for 1.4 x 10(-9) M IT. Mucosal application of 1.0 mM diphenylalamine-2-carboxylic acid (a specific blocker of Cl- channels) after serosal addition of 5 x 10(-8) M AVT or IT inhibited not only the basal but also the stimulated current, revealing a correlation with a hormone-dependent Cl- transport. Specific V1 or V2 receptor analogues of vasopressin (mammalian hormone) were used to characterize the type of neurohypophysial hormone receptors pharmacologically. While the V1 agonist [Phe2,Orn8]-oxytocin stimulated the basal Cl- secretion with a similar profile to that of AVT or IT, the V2 agonist [Deamino1,Val4,d -Arg8]-vasopressin had no effect. The V1 antagonist [d(CH2)5 1,O-Me-Tyr2,Arg8]-vasopressin used at a concentration of 5 x 10(-7) M totally reversed the 10-8 M AVT-stimulated Cl- secretion, whereas the V2 antagonist [d(CH2)5 1,d -Ile2,Ile4,Arg8,Ala9]-vasopressin used at the same concentration had no significant effect. In contrast, similar experiments carried out in the presence of 10(-8) M IT showed that both antagonists significantly reduced the IT-stimulated Cl- secretion, with the efficiency of the V1 receptor antagonist being significantly greater than that of the V2. This study provides evidence for neurohypophysial hormone control of Cl- secretion in fish cultured gill respiratory cells. It suggests that on a physiological basis the hormonal effect is shared by the two peptides present in fish neurohypophysis (AVT and IT), acting by means of two distinct, although pharmacologically similar, V1-type receptors (according to the mammalian classification). These specific receptors are expected to play an important role in controlling ion homeostasis in seawater fish.

Animals↗
PubMed2001

The influence of chylomicron remnants on cholesteryl ester metabolism in cultured rat hepatocytes: comparison of the effects of particles enriched in n-3 or n-6 polyunsaturated fatty acids.

The effect of chylomicron remnants derived from fish oil (rich in n-3 polyunsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids) on the formation and hydrolysis of cholesteryl esters in cultured rat hepatocytes was investigated. Hepatocytes were incubated with or without fish or corn oil chylomicron remnants (0.25-0.75 mM triacylglycerol), and the activity of acyl-CoA:cholesterol acyltranferase (ACAT) and cholesteryl ester hydrolases in the cytosol (cCEH) and endoplasmic reticulum (erCEH), and the expression of mRNA for ACAT1, ACAT2 and cCEH, and of enzyme protein for erCEH was determined. Addition of either type of remnants to hepatocyte cultures resulted in a decreased activity of erCEH, cCEH (after 6 and 19 h incubation), and of ACAT (after 6 h only). Hepatocyte levels of mRNA encoding ACAT1 and ACAT2 were not affected by either type of chylomicron remnants after 6 h of incubation, while ACAT2 mRNA levels were down-regulated by fish oil remnants as compared with corn oil remnants, and also with control cells in the long term (19 h). In contrast, cCEH mRNA levels were down-regulated by chylomicron remnants derived from corn oil but not fish oil. The expression of erCEH protein was induced in response to the inhibitory effect of both types of remnants on the activity of the enzyme, with corn oil remnants having a significantly greater effect. These findings demonstrate that dietary polyunsaturated fatty acids when delivered to hepatocytes in chylomicron remnants regulate the activity of the enzymes governing the intracellular cholesteryl ester balance, and suggest that dietary n-3 and n-6 polyunsaturated fatty acids or a metabolite thereof have differential effects on the expression of their genes at the mRNA and post-transcriptional levels.

Animals↗
PubMed2001

Comparison of the effects of dietary n-3 and n-6 polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants.

The effects of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (derived from fish or corn oil respectively) on the secretion of very-low-density lipoprotein (VLDL) lipid and apolipoprotein B (apoB) by rat hepatocytes in culture was investigated. Remnants were prepared in vivo from chylomicrons obtained from rats given an oral dose of fish or corn oil and incubated with cultured hepatocytes for up to 16 h. The medium was then removed and the secretion of cholesterol and triacylglycerol into the whole medium or the rho<1.050 g/ml fraction during the following 7-24 h was determined. After exposure of the cells to fish-oil as compared with corn-oil remnants, secretion of both cholesterol and triacylglycerol into the whole medium was decreased by 25-35%, and secretion into the rho<1.050 g/ml fraction was decreased by 20-25%. In addition, the levels of apoB48 found in the rho<1.050 g/ml fraction were significantly lower in cells treated with fish-oil rather than corn-oil remnants, although the levels of apoB100 remained unchanged. The expression of mRNA for apoB, as determined by reverse-transcriptase PCR, however, was not significantly changed after exposure of the cells to both types of remnants. These results demonstrate that the effects of dietary n-3 polyunsaturated fatty acids in depressing hepatic VLDL secretion occur directly when they are delivered to the liver from the intestine in chylomicron remnants, and that the secretion, but not the synthesis, of apoB is targeted.

Animals↗
PubMed2001

Oxidation affects the regulation of hepatic lipid synthesis by chylomicron remnants.

The effects of native and oxidized chylomicron remnants on lipid synthesis in normal and oxidatively stressed liver cells were investigated using MET murine hepatocytes (MMH cells), a nontransformed mouse hepatocyte cell line that maintains a highly differentiated hepatic phenotype in culture. Lipid synthesis was determined by measuring the incorporation of [(3)H]oleate into cholesteryl ester, triacylglycerol, and phospholipid by the cells. The formation of cholesteryl ester and phospholipid was decreased by chylomicron remnants in a dose-dependent manner, while triacylglycerol synthesis was increased. Exposure of MMH cells to mild oxidative stress by incubation with CuSO(4) (2.5 microM) for 24 h led to significantly increased incorporation of [(3)H]oleate into triacylglycerol and phospholipid, but not cholesteryl ester, in the absence of chylomicron remnants. In the presence of the lipoproteins, however, similar effects to those found in untreated cells were observed. Oxidatively modified chylomicron remnants prepared by incubation with CuSO(4) (10 microM, 18 h, 37 degrees C) did not influence cholesteryl ester or phospholipid synthesis in MMH cells, but had a similar effect to that found with native remnants on triacylglycerol synthesis. These findings show that hepatic lipid metabolism is altered by exposure to mild oxidative stress and by lipids from the diet delivered to the liver in chylomicron remnants, and these effects may play a role in the development of atherosclerosis.

Animals↗
PubMed2001

Metabolism of chylomicron cholesterol is delayed by estrogen. An in vivo study in the rat.

In order to test the effects of estrogen on the clearance of cholesterol of dietary origin from the blood and its elimination from the body via the bile in an in vivo animal model, the fate of radioactivity from intravenously injected [3H]cholesterol-labeled chylomicrons was investigated in the rat. The labeled lipoproteins were administered intrajugularly to male rats previously given 17alpha ethinyl estradiol or the vehicle only, and the removal of the radioactivity from the blood and its uptake by the liver and secretion into bile was determined. Experiments were carried out in animals with or without prior drainage (20 hr) of the pool of bile acids in the enterohepatic circulation, to take account of the different demands of the liver for cholesterol in the two conditions. In rats without biliary drainage, estrogen treatment decreased the rate of removal of radioactivity from the blood by about 30% and the recovery of cholesterol in the liver by about 50% in the first 30 min after injection of the labeled chylomicrons. After biliary drainage, however, the recovery of label in the liver after 90 min was similar in estrogen-treated and control animals, although its secretion into bile was markedly reduced in the estrogen-treated group (total biliary secretion in 90 min was 26% of the value found in control rats). In addition, the apolipoprotein E (aopE) content of the serum total lipoproteins was markedly reduced by estrogen. These results provide direct evidence indicating that estrogen retards the elimination of dietary cholesterol from the body via the bile in the rat, and this is likely to be mainly due to a reduced level of apoE in chylomicrons. In view of this, we suggest that the hypothesis that estrogen increases the hepatic uptake of chylomicron cholesterol, and its excretion in the bile during contraceptive and hormone replacement therapy should be re-examined.

Animals↗
PubMed2001

Lipid synthesis in macrophages derived from the human cell line THP-1: modulation of the effects of native and oxidized chylomicron-remnant-like particles by oestrogen.

The effects of native and oxidized chylomicron remnants on the synthesis of cholesteryl ester and triacylglycerol in macrophages, and the way that this is influenced by exposure of the cells to oestrogen, was investigated using the human monocyte cell line THP-1 and chylomicron-remnant-like particles containing human apolipoprotein E (CRLPs). Synthesis of the lipids was measured by the incorporation of [(3)H]oleate into cholesteryl ester and triacylglycerol. CRLPs (5-40 microgram of cholesterol/ml) containing either trilinolein or triolein as the triacylglycerol component caused a dose-dependent decrease in cholesteryl ester formation, while triacylglycerol production was unchanged. After oxidation of the CRLPs, the level of thiobarbituric acid-reactive substances was increased by 6.3-fold and 2.2-fold in particles containing trilinolein and triolein respectively. Furthermore, CRLPs containing oxidized trilinolein lost their ability to down-regulate cholesterol esterification, while CRLPs containing oxidized triolein did not. Both types of oxidized CRLPs decreased triacylglycerol synthesis. Treatment of the macrophages with 17beta-oestradiol caused increases of approx. 94% and 34% in the synthesis of cholesteryl ester and triacylglycerol respectively in the absence of CRLPs. The differences between control and oestrogen-treated cells were abolished, however, when CRLPs (40 microgram of cholesterol/ml) were added to the incubations. In addition, in contrast with their lack of effect in control cells, CRLPs containing oxidized trilinolein decreased cholesterol esterification in oestrogen-treated cells by approx. 48%. These findings with CRLPs suggest that chylomicron remnants have significant effects on cholesteryl ester and triacylglycerol synthesis in macrophages, which may be modulated both by the oxidation state of the particles and by oestrogen.

Cell Line↗
PubMed2000

Potassium channels in primary cultures of seawater fish gill cells. I. Stretch-activated K(+) channels.

Previous studies using the patch-clamp technique demonstrated the presence of a small conductance Cl(-) channel in the apical membrane of respiratory gill cells in primary culture originating from sea bass Dicentrarchus labrax. We used the same technique here to characterize potassium channels in this model. A K(+) channel of 123 +/- 3 pS was identified in the cell-attached configuration with 140 mM KCl in the bath and in the pipette. The activity of the channel declined rapidly with time and could be restored by the application of a negative pressure to the pipette (suction) or by substitution of the bath solution with a hypotonic solution (cell swelling). In the excised patch inside-out configuration, ionic substitution demonstrated a high selectivity of this channel for K(+) over Na(+) and Ca(2+). The mechanosensitivity of this channel to membrane stretching via suction was also observed in this configuration. Pharmacological studies demonstrated that this channel was inhibited by barium (5 mM), quinidine (500 microM), and gadolinium (500 microM). Channel activity decreased when cytoplasmic pH was decreased from 7.7 to 6.8. The effect of membrane distension by suction and exposure to hypotonic solutions on K(+) channel activity is consistent with the hypothesis that stretch-activated K(+) channels could mediate an increase in K(+) conductance during cell swelling.

Animals↗
PubMed2000

Potassium channels in primary cultures of seawater fish gill cells. II. Channel activation by hypotonic shock.

Previous studies performed on apical membranes of seawater fish gills in primary culture have demonstrated the existence of stretch-activated K(+) channels with a conductance of 122 pS. The present report examines the involvement of K(+) channels in ion transport mechanisms and cell swelling. In the whole cell patch-clamp configuration, K(+) currents were produced by exposing cells to a hypotonic solution or to 1 microM ionomycin. These K(+) currents were inhibited by the addition of quinidine and charybdotoxin to the bath solution. Isotopic efflux measurements were performed on cells grown on permeable supports using (86)Rb(+) as a tracer to indicate potassium movements. Apical and basolateral membrane (86)Rb effluxes were stimulated by the exposure of cells to a hypotonic medium. During the hypotonic shock, the stimulation of (86)Rb efflux on the apical side of the monolayer was inhibited by 500 microM quinidine or 100 microM gadolinium but was insensitive to scorpion venom [Leirus quinquestriatus hebraeus (LQH)]. An increased (86)Rb efflux across the basolateral membrane was also reduced by the addition of quinidine and LQH venom but was not modified by gadolinium. Moreover, basolateral and apical membrane (86)Rb effluxes were not modified by bumetanide or thapsigargin. There is convincing evidence for two different populations of K(+) channels activated by hypotonic shock. These populations can be separated according to their cellular localization (apical or basolateral membrane) and as a function of their kinetic behavior and pharmacology.

Animals↗
PubMed1999

Regulation of Cl- secretion in seawater fish (Dicentrarchus labrax) gill respiratory cells in primary culture.

1. Primary cultures of sea bass (Dicentrarchus labrax) gill cells grown on permeable membranes form a highly differentiated tight epithelium composed of respiratory-like cells. This preparation was also found to provide a functional model for investigating the hormonal regulation of Cl- secretion. 2. In control conditions, i.e. in the absence of hormones or other stimuli, the cultured epithelium showed a short-circuit current (Isc) of 8.8 +/- 0.4 microA cm-2, a transepithelial potential (Vt) of 28.6 +/- 0.6 mV (serosal side positive), and a transepithelial resistance (Rt) of 5026 +/- 127 Omega cm2. Addition of 50 nM PGE2 caused a stimulation of Isc, Vt and transepithelial conductance, Gt. The increase in Isc was probably due to the elevation in Cl- secretion, since it could be correlated with the stimulation of serosal to mucosal 36Cl- flux. Application of the neurohypophyseal peptide arginine vasotocin (AVT; 50 nM) or the beta-adrenergic agonist isoproterenol (isoprenaline; 0. 5 microM) evoked a stimulation in Cl- secretion, as was shown by the increases in Isc and Gt. The excitatory effect of isoproterenol followed by the inhibitory action of propranolol, a beta-adrenergic antagonist, suggested the presence of beta-adrenergic receptors. Noradrenaline (0.1 microM) elicited a reduction in Isc, Vt and Gt, which was counterbalanced by the addition of phentolamine, an alpha-adrenergic antagonist. This suggested an activation of alpha-adrenergic receptors. 3. This study provides evidence for hormonal control of the Cl- secretion in sea bass gill respiratory cells in culture, involving AVT, prostaglandin (PGE2), and beta- and alpha-adrenergic receptors.

Animals↗
PubMed1999

The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil.

Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body.

Animals↗
PubMed1999

The hepatic uptake of rat high-density lipoprotein cholesteryl ester is delayed after treatment with cholesteryl ester transfer protein.

The effects of cholesteryl ester transfer protein (CETP) on the direct uptake of HDL cholesteryl ester by the liver was investigated using the rat in vivo and the isolated perfused rat liver as experimental models. Rat plasma was incubated with [3H]cholesterol in the presence or absence of partially purified human CETP for 18 hr and [3H] cholesteryl ester-labeled HDL was then isolated by ultracentrifugation. The CETP-treated as compared to untreated HDL showed a small shift toward a lower density in the peak of lipoprotein cholesterol, suggesting that the HDL particle size was increased. After injection of the labeled HDL into rats in vivo, more radioactivity remained in the plasma after 60 min when the CETP-treated preparation was used, but the amounts found in the liver and secreted in the bile were not significantly different from those obtained with the untreated HDL. The distribution of the label remaining in the plasma after 60 min between different density fractions corresponding to HDL subclasses suggested that the uptake of HDL2 and HDL3 was delayed by CETP treatment. Radioactivity from CETP-treated HDL was also removed from the perfusate of isolated perfused rat livers more slowly than that from untreated HDL, and in this case the amount found in the liver after 60 min was significantly lower. These findings indicate that treatment with CETP has a direct inhibitory effect on the clearance of rat HDL cholesteryl ester from the blood and its uptake by the liver.

Animals↗
PubMed1998

The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat.

The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in long chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days. The secretion of radioactivity into bile as both bile acids and unesterified cholesterol was significantly slower in the animals fed palm oil as compared to those given olive or corn oil, indicating that dietary saturated fat retards the excretion of cholesterol from the diet as compared to mono- or n-6 polyunsaturated fat. In order to investigate the mechanisms underlying these differences, the influence of the three high fat diets on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis in the liver and on biliary lipid output were also measured. The ratio of cholesterol esterification to cholesteryl ester hydrolysis was markedly raised in the olive and corn oil-fed as compared to palm oil-fed animals. Biliary cholesterol secretion was higher in corn oil-fed rats than in those fed olive or palm oil or a low fat diet, and this was associated with a markedly increased lithogenic index in these animals. The activity of cholesterol 7alpha hydroxylase was higher in the olive and corn oil-fed than in the palm oil-fed animals, although the expression of mRNA for the enzyme was increased only in the olive oil diet group. After 20 h biliary drainage, the rate of bile acid secretion into bile was increased in the rats fed olive and corn oil rather than to palm oil. These findings indicate that feeding rats mono- or n-6 polyunsaturated as compared to saturated fat in the diet promotes the storage of cholesteryl ester in the liver and leads to increased bile acid synthesis, resulting in the more rapid excretion of cholesterol originating from the diet via the bile.

Animals↗
PubMed1998

The mechanism underlying the hypocholesterolemic effect of chronic fish oil feeding in rats is not due to increased excretion of dietary cholesterol.

The role of the excretion of dietary cholesterol in the hypocholesterolaemic effect of chronic fish oil feeding in rats was investigated. The hepatic uptake and processing of [3H]cholesterol carried in chylomicrons derived from fish oil was studied in vivo in rats fed a low fat diet or a diet supplemented with fish oil for 21 days. In addition, the effects of the fish oil diet on cholesterol esterification, cholesteryl ester hydrolysis, bile acid synthesis and biliary lipid secretion were determined. In rats fed the fish oil as compared to the low fat diet, the uptake of [3H]cholesterol from the blood and its secretion into bile as bile acids was significantly slower, and this was entirely due to a decrease in the bile acid fraction. Biliary bile acid mass secretion was unchanged by fish oil feeding, while biliary cholesterol and phospholipid secretion was increased. No significant differences were observed either in the expression of mRNA for cholesterol 7alpha hydroxylase or the secretion of bile acids into bile after 20 h biliary drainage between the fish oil and low fat diet groups, suggesting that bile acid synthesis is not affected. These results indicate that the access of chylomicron cholesterol to the hepatic substrate pool for bile acid formation is decreased in the fish oil fed rats, and this, together with its slower uptake from the blood, accounts for the retardation of its excretion via the bile. Thus, the hypocholesterolemic effect of dietary fish oil in rats is not due to more rapid metabolism of cholesterol originating from the diet.

Animals↗
PubMed1997

The lipolysis of chylomicrons derived from different dietary fats by lipoprotein lipase in vitro.

The lipolysis of chylomicrons derived from palm, olive, corn or fish oil (enriched in saturated, monounsaturated, n - 6 polyunsaturated and n - 3 polyunsaturated fatty acids, respectively) by rat post-heparin lipoprotein lipase in vitro was compared by measuring the release of [3H]oleate from their triacylglycerol. Chylomicrons derived from corn oil were lipolysed more rapidly than the other types in the first 20 min of the reaction, but after 120 min the total amount of triacylglycerol hydrolysed was similar with all types of chylomicrons used. The rate of lipolysis of the different types of chylomicrons also showed different dependencies on the substrate concentration. The highest Vmax values were obtained when the chylomicrons were derived from olive and corn oil and the lowest when they were derived from palm oil, while olive oil chylomicrons gave the highest Km and palm oil chylomicrons the lowest. These results indicate that differential metabolism of chylomicrons of different fatty acid composition by lipoprotein lipase may play a part in the differential rates of clearance from the blood of lipid of dietary origin demonstrated in earlier work from our laboratory.

Animals↗
PubMed1997

Comparison of the uptake and processing of cholesterol from chylomicrons of different fatty acid composition in rats fed high-fat and low-fat diets.

The fate of [3H]cholesterol carried in chylomicrons prepared from rats given a meal of palm oil (rich in long-chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids) was investigated in vivo in rats fed a low-fat diet or a diet supplemented with the corresponding oil (to provide 40% of the calories) for 21 days. In the low-fat-fed groups, radioactivity was removed from the blood and secreted into bile over 180 min more rapidly when the chylomicrons were derived from corn oil as compared to palm or olive oil. After feeding the corresponding high-fat diets, however, both parameters were decreased in rats fed palm and corn oil, but not olive oil. As a result of these changes, the rates of removal of radioactivity from the blood and secretion into bile were similar in animals given the olive oil and corn oil diets, and higher than those in rats fed the palm oil diet. All the high-fat diets tended to increase the proportion of the radioactivity in the plasma found in the 1.006-1.050-g/ml fraction (low-density lipoprotein) and decrease that in the 1.050-1.25-g/ml (high-density lipoprotein) fraction in comparison to the respective low-fat diet groups, but the transfer of radioactivity to the plasma high-density lipoprotein fraction was particularly slow in palm-oil-fed rats. These findings indicate that diets high in saturated or n-6 polyunsaturated fat retard the metabolism of chylomicron cholesterol in comparison to diets low in fat, while those high in monounsaturated fat do not have this effect. As a consequence of this, the rate of removal of cholesterol of dietary origin from the body is slower in animals fed saturated as compared to monounsaturated or n-6 polyunsaturated fat. Thus, differential metabolism of chylomicron cholesterol clearly plays an important role in the hyper- and hypo-cholesterolaemic effects of these dietary fats.

Animals↗