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PubMed2002

Endotoxin-lipoprotein complex formation as a factor in atherogenesis: associations with hyperlipidemia and with lecithin:cholesterol acyltransferase activity.

A potential role of endotoxin-lipoprotein (bacterial lipopolysaccharide-lipoprotein, LPS-LP) complex formation as a pathogenic factor for atherosclerosis has not been studied yet. The aim of this study was to test the hypothesis that in endotoxinemia in humans hyperlipidemia associated with atherosclerosis development can favor an excessive LPS-LP complex formation, and endotoxin presented in blood can inhibit lecithin:cholesterol acyltransferase (LCAT), one of the key enzymes of reverse cholesterol transport. Endotoxin-binding capacity of lipoproteins (LP) in patients with normolipidemia and hyperlipidemia types IIa and IV was estimated from label incorporation into different LP fractions isolated by means of sequential ultracentrifugation following serum preincubation with Salmonella minnesota R595 125I-labeled LPS. The effect of varied concentrations of S. minnesota R595 LPS on LCAT activity was evaluated from the overall esterifying activity of serum using [1,2-3H2]cholesterol-labeled substrate. The elevation of low density LP (LDL) and very low density LP (VLDL) contents in blood serum in hyperlipidemia types IIa and IV, respectively, resulted in significant elevation of LPS binding to these fractions. LPS added to the blood serum leads to the dose-dependent decrease in LCAT activity. The revealed phenomena of elevated LPS binding to atherogenic LP fractions in hypercholesterolemia and endotoxin-induced LCAT inhibition suggest the pathogenic role of LPS-LP complexes in atherogenesis.

Arteriosclerosis↗
PubMed2001

Reduction in serum lecithin:cholesterol acyltransferase activity in natural cases of pneumonia in calves.

In experimental calf pneumonia induced by inoculations of Pasteurella haemolytica or bovine herpesvirus-1, lipoprotein lipid concentrations and lecithin:cholesterol acyltransferase (LCAT) activity decrease. The purpose of this study was to examine whether similar changes in lipoproteins occur in natural cases of calf pneumonia. When monitored in a time-course study, the activity of LCAT, and the concentrations of free cholesterol, cholesteryl esters, phospholipids and triglycerides were steadily decreased. No significant decreases in LCAT activity or lipid concentrations were detected in sera from cows with mastitis. These results, coupled with the previous findings on experimental calf pneumonia, indicate that, while decreases in LCAT activity and the LCAT-related lipid concentrations are involved in the pathogenesis of calf pneumonia, this is not the case for all inflammatory diseases.

Animals↗
PubMed1997

Decreased serum lecithin:cholesterol acyltransferase activity in spontaneous cases of fatty liver in cows.

Lecithin:cholesterol acyltransferase (LCAT) activity in serum was evaluated in spontaneous cases of fatty liver in cows. The enzyme activity of 631 +/- 62 U (mean +/- SEM, decrease in nmol of free cholesterol per h per ml of serum) in cows with fatty liver (n = 16) was significantly (p < 0.01) lower than that in cows without fatty liver (979 +/- 22 U; n = 16). In addition to the decrease in LCAT activity, the concentrations of phosphatidylcholine (a fatty aryl donor for esterification of free cholesterol) and of cholesteryl esters (products of the LCAT reaction) were reduced in the high-density lipoprotein fractions from cows with fatty livers. The concentrations in the serum of apolipoprotein A-I, an activator of LCAT, was also reduced in cows with fatty livers. These results suggest that the decreased LCAT activity, which may be attributable to impaired hepatic secretion or to the suppression of the activity in the plasma by reduced concentrations of phosphatidylcholine and apolipoprotein A-I, resulted in the lower concentrations of cholesteryl esters. Because cholesteryl esters are utilized in steroidogenic tissues for the synthesis of steroid hormones such as progesterone and glucocorticoids, and insufficient supply of the cholesterols may be of relevance to the reduced fertility and immune competence observed in cows with fatty livers.

Animals↗
PubMed2000

Overexpression of human lecithin:cholesterol acyltransferase in mice offers no protection against diet-induced atherosclerosis.

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol. We have used homozygous transgenic mice overexpressing the human LCAT transgene to study the effect of a "Western-type" atherogenic diet (30% fat, 5% cholesterol and 2% cholic acid) on their LCAT expression, activity, lipoprotein profile and tendency to develop atherosclerosis. The LCAT activity was 35-fold higher in serum of the homozygous transgenic mice than in murine control serum, and decreased 11-20% in the transgenic mice when fed the atherogenic diet. The total cholesterol and high-density lipoprotein cholesterol (HDL-C) concentrations were approximately doubled in the transgenic mice compared with the controls when both groups were fed a regular chow diet. In mice on the atherogenic diet, the triglyceride concentration decreased about 50% to the same level in transgenic and control mice. Total cholesterol and HDL-C concentrations increased and were 60-80% higher in the transgenic mice. The expression of LCAT mRNA in the liver was decreased by 49-60% in the transgenic mice when fed the atherogenic diet. The development of atherosclerosis was similar in transgenic and control mice. Thus, the 14- to 27-fold higher LCAT activity and the higher HDL-C concentrations in the homozygous LCAT transgenic mice had no significant protective influence on the development of diet-induced atherosclerosis.

Animals↗
PubMed2001

Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy.

The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.

Acyltransferases↗
PubMed1993

Role of elevated lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein activities in abnormal lipoproteins from proteinuric patients.

Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of free cholesterol, and the distribution of cholesteryl ester among lipoproteins in plasma. Alterations in these processes may play a role in the lipoprotein abnormalities associated with glomerular proteinuria. The activities of LCAT and CETP were measured using excess exogenous substrate assays in nine patients with nephrotic-range proteinuria and in 18 matched controls. The proteinuria-lowering effect of four weeks of angiotensin converting enzyme (ACE) inhibition with enalapril was also studied. Plasma very low lipoprotein and low density lipoprotein (VLDL and LDL) cholesterol, triacylglycerol and apolipoprotein B levels were significantly elevated in the patients compared with controls. High density lipoprotein (HDL) total cholesterol, free cholesterol, cholesteryl ester and the free cholesterol/cholesteryl ester ratio in HDL were lower. Total plasma apolipoprotein A1 was normal. Plasma LCAT and CETP activities were elevated in the patients by 30% (P < 0.01) and by 39% (P < 0.01), respectively, and were both inversely related to serum albumin. VLDL and LDL cholesterol levels were positively related to LCAT and CETP activities, whereas the HDL free cholesterol content was inversely related to LCAT activity. ACE inhibition resulted in a 40% reduction of proteinuria, a partial normalization of LCAT activity, and a decrease in VLDL and LDL cholesterol. In conclusion, elevated activities of LCAT and CETP may provide a mechanism that contributes to the low proportion of cholesterol in HDL relative to that in VLDL and LDL, as well as to the compositional changes of HDL seen in glomerular proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase.

A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels.

Animals↗
PubMed2004

Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans.

OBJECTIVE: Increased HDL-cholesterol (HDL-C) concentrations have been associated with lower coronary heart disease risk. On the other hand, dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids that are substrates of lecithin cholesterol acyltransferase (LCAT), an important enzyme in HDL metabolism. The purpose of this study was to examine the association between the saturated fatty acid (SFA) intake and LCAT activity. DESIGN: An interventional study was performed in a monk community of 25 men. SETTING: A French monk community, South West of France. SUBJECTS AND INTERVENTIONS: The basal diet of the study cohort contained SFA in a proportion of 13.5% of their total energy intake (TEI). They were submitted to two experimental isocaloric diets containing either 8.4% of the TEI in SFA (diet A) or 11% (diet B), each lasting 5 weeks. RESULTS: The elevation of SFA in diet B was mainly obtained by decreasing carbohydrates. The only significant difference among total fats between diets A and B was the myristic acid content (0.6 and 1.2% of TEI, respectively). The elevation in SFA in diet B resulted in a significant increase of HDL-C (P<0.04), while plasma apo A-I concentration and LCAT activity both decreased (P<0.02). CONCLUSION: Altogether, these results are consistent with a negative effect of SFA on reverse cholesterol transport.

Adult↗
PubMed1998

Efficient coexpression and secretion of anti-atherogenic human apolipoprotein AI and lecithin-cholesterol acyltransferase by cultured muscle cells using adeno-associated virus plasmid vectors.

Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attractive targets for prevention or treatment of atherosclerosis. With the eventual aim of safe and efficient gene delivery to skeletal muscle, our chosen secretory platform for systemic delivery of anti-atherogenic proteins, we have constructed conventional and AAV-based plasmid vectors containing human apoAI or LCAT cDNAs; their efficacy was tested by lipoplex transfection of mouse C2C12 muscle cells or human 293 cells. The secretion of apoAI or LCAT by transduced cultures was two- to five-fold higher using AAV-based plasmid vectors than conventional plasmid vectors. Additionally, cells transfected with a bicistronic AAV-based vector containing an internal ribosome entry site (IRES) efficiently expressed both apoAI and LCAT simultaneously. Furthermore, AAV-based vector sequences were retained by host cells, whereas those of conventional plasmid vectors were lost. These studies indicate that ectopic overexpression of apoAI and LCAT in muscle tissue using AAV-based plasmid vectors might provide a feasible anti-atherogenic strategy in vivo.

Animals↗
PubMedDate not supplied

Neonatal outcome when delivery follows a borderline immature lecithin to sphingomyelin ratio.

OBJECTIVE: Occasionally, clinicians are presented with a complicated preterm pregnancy where fetal pulmonary maturity testing might be used to help guide management decisions. However, should delivery be allowed if the lecithin to sphingomyelin ratio (L/S ratio) is not quite mature? The incidence of newborn complications after delivery with L/S ratio values of 1.8 and 1.9 is unknown. The purpose of this study was to evaluate the neonatal morbidity and mortality in patients that delivered with these borderline immature results. STUDY DESIGN: All patients who underwent fetal pulmonary maturity testing were prospectively recorded in log books. An L/S ratio of > or = 2.0 was considered mature. Patients with an L/S ratio of 1.8 or 1.9 were considered "borderline immature." These borderline immature cases were evaluated for the gestational age at amniocentesis, the gestational age at delivery, and neonatal outcome. RESULTS: During the 9-year study period, L/S ratio testing was performed on 2038 patients. Of these, 162 preterm patients (7.9%) had an L/S ratio of 1.8 or 1.9 A total of 63 of these 162 patients delivered < 72 hours after the amniocentesis and met study criteria. The pregnancies ranged from 27 to 36 weeks' gestation. There was a 13% incidence (95% confidence interval (CI) of 4% to 30%) of major neonatal morbidity and a 3% incidence (95% CI of 0% to 17%) of neonatal mortality in the 30 pregnancies with an L/S ratio of 1.8. The incidence of major neonatal morbidity was only 3% (95% CI of 0% to 15%) in the 33 patients with an L/S ratio of 1.9, with no cases of mortality (95% CI of 0% to 9%). CONCLUSION: Based on 95% CIs, the data of this study reveal that the maximum risk for major morbidity is < or = 15%, with a mortality risk of < 10% in a preterm newborn delivered with a 1.9 L/S ratio value. The maximum risk is 30% for major morbidity and 17% for mortality in preterm newborns delivered with a 1.8 L/S ratio. This information may help in the decision-making process of whether to deliver or to observe when faced with a borderline immature L/S ratio result in a complicated preterm pregnancy.

Amniocentesis↗
PubMed2002

Role of the interfacial binding domain in the oxidative susceptibility of lecithin:cholesterol acyltransferase.

We had previously shown that the cholesterol esterification activity of lecithin:cholesterol acyltransferase (LCAT) is destroyed by oxidation, but still it retains the ability to hydrolyse water-soluble substrates. This suggested that the inactivation of the enzyme is not due to its catalytic function, but due to a loss of its hydrophobic binding. Since recent studies have shown that a tryptophan residue in the putative interfacial domain (Trp(61)) is critical for the activity, we determined the possible role of this residue in the oxidative susceptibility and substrate specificity of LCAT by site-directed mutagenesis. Deletion of Trp(61) resulted in a 56% loss of cholesterol esterification (LCAT) activity, but the phospholipase A(2) (PLA(2)) and the esterase activities of the enzyme were stimulated slightly. Replacing Trp(61) with another aromatic residue [Trp(61)-->Tyr (W61Y)] resulted in an increase in all activities (14-157%), whereas replacing it with an aliphatic residue [Trp(61)-->Gly (W61G)] caused a dramatic loss of LCAT (-90%) and PLA(2) (-82%) activities, but not the esterase activity (-5%). W61Y was the most sensitive to oxidation, whereas W61G was the most resistant, with respect to the LCAT and PLA(2) activities. However, the activities which do not involve interfacial binding, namely the esterase activity and the transesterification of short-chain phospholipids, were more resistant to oxidation in all LCATs, indicating a selective loss of the interfacial binding by oxidation. Furthermore, replacing the two cysteines (Cys(31) and Cys(184)) in the Trp(61) deletion mutant caused additional resistance of the enzyme to oxidizing agents, showing that both domains of the enzyme contribute independently to its oxidative susceptibility. Since the hydrolysis of truncated phospholipids, generated during the oxidation of low-density lipoproteins, does not require the interfacial-binding domain, our results suggest that LCAT may take part in the detoxification of these compounds even after the loss of its cholesterol esterification function.

Animals↗
PubMed2002

Cloning and molecular expression analysis of large and small lecithin:retinol acyltransferase mRNAs in the liver and other tissues of adult rats.

Retinyl ester, the most abundant form of vitamin A (retinol), is synthesized by the enzyme lecithin:retinol acyltransferase (LRAT). Previously, we cloned a 2.5 kb LRAT cDNA from rodent liver which codes for functional LRAT activity. However, Northern blots of tissues probed with the 2.5 kb cDNA revealed the presence of a larger transcript of approximately 5 kb as well as several smaller transcripts. To elucidate the nature of the large LRAT transcript, a high-molecular-mass adrenal gland cDNA library was screened. Two similar clones of 3962 and 3187 nt were identified which appeared to be part of the 3'-untranslated region (UTR) of a 5358 nt LRAT mRNA. The 5.3 kb cDNA was then amplified from liver by reverse transcriptase PCR (RT-PCR) and demonstrated to encode functional LRAT activity. The 3'-UTR of the 5.3 kb cDNA contains several AAUAAA polyadenylation signals. Analysis of the 3' ends of LRAT mRNA transcripts from liver, intestine and testis showed the usage of both canonical and non-canonical polyadenylation signals. To further analyse the LRAT mRNAs expressed in vivo, Northern blot analysis was performed using four probes spanning sections from the 5' end to the distal 3' end of the 5.3 kb LRAT cDNA. The results show that the major 5.3 kb transcript uses the canonical signal AAUAAA located at nt 5308, and the major short transcript of approximately 1.5 kb uses the non-canonical signal AUUAAA located at nt 1330. The 5.3 kb LRAT transcript was predominant in the liver of retinoic acid-repleted vitamin A-deficient rats, coincident with increased quantitative expression of LRAT mRNA and enzyme activity. The differential usage of these polyadenylation signals can explain the presence of multiple LRAT mRNA transcripts which are expressed in different tissue-specific patterns.

3' Untranslated Regions↗
PubMed1993

Retinol esterification in bovine retinal pigment epithelium: reversibility of lecithin:retinol acyltransferase.

Esterification of all-trans-retinol is a key reaction of the vertebrate visual cycle, since it produces an insoluble, relatively non-toxic, form of the vitamin for storage and supplies substrate for the isomerization reaction. CoA-dependent and -independent pathways have been described for retinol esterification in retinal pigment epithelium (RPE). The CoA-independent reaction, catalysed by lecithin:retinol acyltransferase (LRAT) was examined in more detail in this study. Addition of retinol to RPE microsomes results in a burst of retinyl ester synthesis, followed by a rapid apparent cessation of the reaction. However, [3H]retinol, added when retinyl ester synthesis has apparently ceased, is rapidly incorporated into retinyl ester without a net increase in the amount of ester. The specific radioactivities of [3H]retinol and [3H]retinyl ester reach the same value. [14C]Palmitate from palmitoyl-CoA is incorporated into preexisting retinyl ester in the absence of net ester synthesis, too. These exchange reactions suggest that the reaction has reached equilibrium at the plateau of the progress curve and that only the accumulation of retinyl ester, and not its synthesis, has stopped during this phase of the reaction. Studies with geometrical isomers of retinol revealed that the rate of exchange of all-trans-retinol with all-trans-retinyl esters was about 6 times more rapid than exchange of 11-cis-retinol with 11-cis-retinyl ester. This is the first demonstration of the reversibility of LRAT and the first example of stereospecificity of retinyl ester synthesis in the visual system. Reversal of the LRAT reaction could contribute to the mobilization of 11-cis-retinol from 11-cis-retinyl ester pools.

Acyltransferases↗
PubMed1993

Plasma activities of lecithin:cholesterol acyltransferase, lipid transfer proteins and post-heparin lipases in inbred strains of rabbits hypo- or hyper-responsive to dietary cholesterol.

Plasma lipoproteins, plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP) and post-heparin lipases were measured before and after cholesterol challenge in two inbred strains of rabbits with either a high (hyper-responders) or a low (hyporesponders) response of plasma cholesterol to dietary cholesterol. The purpose of this study was to provide clues about the mechanisms underlying the effect of dietary cholesterol on lipoprotein levels and composition, and particularly those underlying the strain difference of this effect. Cholesterol feeding (0.15 g of cholesterol/100 g of diet) caused increased plasma total cholesterol concentrations and an increased ratio of cholesteryl esters:triacylglycerol in all lipoprotein particles in both strains; these effects were significantly greater in hyper- than hypo-responsive rabbits. Feeding on the high-cholesterol diet lowered plasma triacylglycerols in hyper-responders, but caused increased plasma triacylglycerol levels in hyporesponders. This was accompanied by significantly greater increases in the activities of hepatic triacylglycerol lipase and lipoprotein lipase in hyper- than in hypo-responders. Both strains showed a dietary-cholesterol-induced rise in plasma CETP as well as in PLTP activity. The increase in PLTP activity was greater in the hyper-responders, but that of CETP was less. There was no effect of dietary cholesterol on LCAT activity. It is hypothesized that the lipases are involved in the removal of cholesterol-rich lipoproteins.

Animals↗
PubMed1993

Lecithin:cholesterol acyltransferase: role of N-linked glycosylation in enzyme function.

Lecithin:cholesterol acyltransferase (LCAT; phosphatidylcholine-sterol acyltransferase, EC 2.3.1.43) is a glycoprotein which is responsible for the formation of cholesteryl ester in plasma. The carbohydrate content has been estimated to be approx. 25% of the total LCAT mass, and four potential N-linked glycosylation sites have been predicted at residues 20, 84, 272 and 384 of the LCAT protein sequence. In the present study, we have examined which of these sites are utilized and how the N-glycosylation affects the secretion and function of the enzyme. Site-directed mutagenesis was performed to eliminate the glycosylation consensus sequence at each of the four potential sites, and the mutant proteins were expressed in COS cells. The amount of each mutant LCAT secreted was similar to that of the wild-type enzyme but the molecular mass was decreased by 3-4 kDa. The specific activity of each mutant LCAT was significantly different from the wild-type; however, the magnitude and direction of the change depended on the glycosylation site mutagenized. Loss of carbohydrate at position 20, 84 or 272 resulted in a decrease in the specific activity of the mutant enzymes by 18%, 82%, and 62% respectively. In contrast, the mutant protein without glycosylation at position 384 displayed a 2-fold increase in enzyme activity. In addition, a quadruple mutant was constructed such that all four potential glycosylation sites were eliminated. The amount of the unglycosylated LCAT secreted into the culture medium was less than 10% of the wild-type level and the specific activity of this enzyme was decreased to 5% of that of the wild type. The results demonstrate that all four potential N-glycosylation sites in LCAT are used and the presence of carbohydrate at each site has diverse effects on the enzyme activity.

Animals↗
PubMed1995

Secretion of active human lecithin-cholesterol acyltransferase by insect cells infected with a recombinant baculovirus.

Difficulties in purifying the plasma enzyme lecithin-cholesterol acyltransferase (LCAT) have hampered detailed studies of its (patho)physiological role in lipoprotein metabolism and of structure-function relationships. Potentially, baculovirus-driven expression systems offer a powerful means to produce significant amounts of LCAT. Accordingly, full-length LCAT cDNA was cloned into pVL 1392, a high-level expression derivative of Autographa californica nuclear polyhedrosis virus (AcNPV), and the resultant plasmid was co-transfected into Trichoplusia ni insect cells (High 5 line) with a linearized viral DNA using lipofectin. Such viral DNA had a lethal mutation and grew only when recombined with a pVL1392-type rescue plasmid; cells infected with recombinant Autographa californica LCAT virus changed from a fibroblast-like morphology to rounded, but lacked the polyhedrin occlusion bodies characteristic of wild-type AcNPV infections. Enzymically active recombinant LCAT (rLCAT), sensitive to sulphydryl reagents, was secreted in the late phase of infection (36-48 h) but was absent with wild-type infections. The secreted protein had an apparent molecular mass of 53 kDa by SDS/PAGE, lower than that of native plasma LCAT; it was susceptible to endoglycosidase H digestion and was bound by concanavalin A, suggesting that precursor high-mannose N-glycan chains had not undergone full maturation to complex types. Pretreatment of the cells with tunicamycin to inhibit the first step of N-glycosylation led to intracellular accumulation of immature rLCAT (approximately 46-48 kDa) and a marked reduction in enzyme secreted. We conclude that the baculovirus gene-expression system will permit production of biologically active normal and mutant forms of LCAT protein.

Animals↗
PubMed1995

Partial characterization of regulation of biliary lecithin hydrophobicity: association with organic anion-induced solute cholestasis in rats.

We examined the effects of the depletion of bile salts and of the intravenous infusion of sodium taurocholate (STC) with or without bromosulphophthalein (BSP) in rats on the biliary secretion of lipids to clarify the regulatory mechanism(s). Each rat was equipped with a bile-duct cannula to collect bile. After the endogenous bile salt pool was depleted, STC was infused at a constant rate (160 nmol/min per 100 g body wt.) with or without BSP (50, 100, or 150 nmol/min per 100 g body wt.). BSP reduced the biliary secretion of cholesterol and phospholipids dose-dependently without affecting the secretion of bile salts (uncoupling phenomenon). Compared with the physiological and STC-infused condition, the biliary cholesterol/phospholipid ratio and saturated/unsaturated fatty acid ratio increased under the bile salts depletion and uncoupling phenomenon. Data indicate that the hydrophobicity of biliary lecithin increases with a decrease in the bile salt micelle capacity to induce biliary lipid secretion, resulting in a higher packing density of biliary vesicle. The cholesterol-holding capacity of the biliary vesicle is therefore enhanced during the depletion of bile salts and the uncoupling phenomenon.

Animals↗
PubMed1979

Lecithin-cholesterol acyltransferase and the lipoprotein abnormalities of parenchymal liver disease.

1. Detailed studies have been made of the plasma lipoprotein abnormalities in parenchymal liver disease to test the hypothesis that the abnormalities would correlate with plasma lecithin-cholesterol acyltransferase (LCAT) activity. 2. When LCAT was high, very-low-density-lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility. When LCAT was low, VLDL concentrations were greatly reduced. 3. With high LCAT low-density lipoproteins (LDL) were normal. The LDL particles found with low LCAT activity were of normal size but of abnormal composition, being triglyceride rich and cholesteryl ester poor. Regardless of LCAT activity LDL were present in normal amounts. 4. High-density lipoproteins (HDL) were normal in composition and electron-microscopic appearance when LCAT activity was high. When LCAT activity was low HDL were abnormal in composition and 'stacked discs' were seen on electron microscopy. 5. These results suggest that low LCAT activity may be the cause of at least some of the lipoprotein changes of parenchymal liver disease.

Adult↗