Formation of lipoprotein-X. Its relationship to bile compounds.

Manzato, Enzo; Fellin, Renato; Baggio, G.; Walch, Stephan G.; Neubeck, W; Seidel, D.

doi:10.1172/jci108393

Cited by 139 publications

(67 citation statements)

References 36 publications

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“…This causes plasma CH to rise by ill-defined mechanisms; synthesis may be increased (6). Lp-X also results from retention of biliary lipid (16). These abnormalities were seen in both of our patients, and both promptly recovered after surgery.…”

Section: Resultssupporting

confidence: 63%

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Correctable Plasma Lipoprotein Abnormalities in Infants with Choledochal Cysts

et al. 1985

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ABSTRACT. Plasma lipoproteins from two female patients-patient A, 4 wk and patient B, 19 months-were examined prior to and at 1 and 5 wk after surgical correction of biliary obstruction due to choledochal cyst. The findings were correlated with standard indices of hepatic function, namely SGPT, GGTP, S'nucleotidase, serum bile salts, and total and conjugated bilirubin. Prior to surgery in both patients plasma cholesterol, phospholipid, and triglyceride were elevated; cholesterol esters were low; high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I, the major protein constituent of HDL, were subnormal; most of the plasma lipids were contained in the low-density lipoprotein density region; lipoprotein-X was present. Patient B had had a relatively brief obstruction and suffered little secondary hepatic injury. One week after surgery, plasma lipid concentrations returned to normal; apoliprotein A-I increased in the HDL density region and a concomitant rise in cholesterol esters to near normal, 65%, was observed; plasma lipids were contained predominantly in HDL; hepatic function improved markedly. Patient A had had intrauterine obstruction and suffered major hepatic injury with cirrhosis. One week after surgery, plasma lipid concentrations, cholesterol esters, low-density lipoprotein lipid predominance, and hepatic function remained essentially unchanged. Five weeks after surgery, the lipoprotein levels and composition and hepatic function were near normal. In conclusion, children with biliary obstruction have lipoprotein abnormalities similar to those seen in adult patients.

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Section: Resultssupporting

confidence: 63%

“…Most of the PL is found in fractions 1-13. There is very little CH in the "heavy" HDL region of the gradient (fractions [14][15][16][17][18][19][20]. The small amount of apo A-I detected in the gradient is found only in the "heavy" HDL and plasma protein pool region.…”

Section: Resultsmentioning

confidence: 99%

Correctable Plasma Lipoprotein Abnormalities in Infants with Choledochal Cysts

et al. 1985

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“…Several decades ago, the aberrant mobility of plasma lipoproteins from cholestatic patients was already demonstrated via agarose electrophoresis (2) and gradient ultracentrifugation (3). Upon agarose electrophoresis, human LpX migrates toward the anode more slowly than all normal lipoproteins, and on agar electrophoresis it may even migrate toward the cathode (4,5). Upon gradient ultracentrifugation, LpX sediments in the LDL fraction (3).…”

Section: Introductionmentioning

confidence: 99%

“…Using smallangle X-ray scattering, it was shown that LpX, in contrast to the normal serum lipoproteins, is a unilamellar vesicle with an aqueous lumen (6,7). It was postulated that LpX particles represent biliary vesicles, which are regurgitated into the plasma of cholestatic subjects (5). This hypothesis is plausible because LpX particles and biliary lipid vesicles are both lipsomes which almost exclusively contain phosphatidylcholine and free cholesterol (8).…”

Section: Introductionmentioning

confidence: 99%

Class III P-glycoproteins mediate the formation of lipoprotein X in the mouse.

Elferink¹,

Ottenhoff²,

Marle³

et al. 1998

J. Clin. Invest.

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Cholestasis is associated with hypercholesterolemia and appearance of the abnormal lipoprotein X (LpX) in plasma. Using mice with a disrupted Mdr2 gene, we tested the hypothesis that LpX originates as a biliary lipid vesicle. Mdr2-deficient mice lack Mdr2 P-glycoprotein, the canalicular translocator for phosphatidylcholine, and secrete virtually no phospholipid and cholesterol in bile. Bile duct ligation of Mdr2 ϩ / ϩ mice induced a dramatic increase in the plasma cholesterol and phospholipid concentration. Agarose electrophoresis, density gradient ultracentrifugation, gel permeation, and electron microscopy revealed that the majority of phospholipid and cholesterol was present as LpX, a 40-100 nm vesicle with an aqueous lumen. In contrast, the plasma cholesterol and phospholipid concentration in Mdr2 Ϫ / Ϫ mice decreased upon bile duct ligation, and plasma fractionation revealed a complete absence of LpX. In mice with various expression levels of Mdr2 or MDR3 , the human homolog of Mdr2 , we observed that the plasma level of cholesterol and phospholipid during cholestasis correlated very closely with the expression level of these canalicular P-glycoproteins. These data demonstrate that during cholestasis there is a quantitative shift of lipid secretion from bile to the plasma compartment in the form of LpX. The concentration of this lipoprotein is determined by the activity of the canalicular phospholipid translocator. ( J. Clin. Invest. 1998. 102:1749-1757.)

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“…This is reminiscent of other scenarios in which biliary lipid outputs are impeded either through bile duct ligation ( 30,31 ) or due to biliary cholestasis ( 28,42 ), and plasma free cholesterol and phospholipids are consequently elevated. Under those circumstances, the excess free cholesterol and phospholipids circulate on an abnormal lipoprotein termed "lipoprotein X," which appear as lamellar structures under the electron microscope ( 42 ). Interesting, we have reported the existence of lamellar lipoproteins in Pltp KO mice fed COD ( 2 ), and we observed these particles in COD-fed Pltp KO/ Apoe KO as well ( Fig.…”

Section: Discussionmentioning

confidence: 91%

Diet-induced lipid accumulation in phospholipid transfer protein-deficient mice: its atherogenicity and potential mechanism

Yeang

Qin

Chen

et al. 2010

Journal of Lipid Research

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transfer of free cholesterol ( 3 ). Moreover, PLTP has been implicated in hepatic apoB-containing particle secretion ( 4 ). Consistent with its role in lipoprotein metabolism, Pltp is regulated by liver X receptor (LXR) ( 5 ) and farnesoid X receptor (FXR) ( 6 ), which are regulators of bile metabolism. Pltp overexpression has been associated with increased cholesterol and phospholipids output via the bile ( 7 ).PLTP defi ciency in mice results in a large decrease in plasma lipid levels, including total cholesterol, cholesteryl ester, and phospholipids, when the mice are fed a chow diet ( 2, 8 ) or Western-type diet consisting of 20% milk fat plus 0.15% cholesterol ( 8 ). However, when fed a high-fat diet consisting of 20% saturated fat from coconut oil and 0.15% cholesterol (COD), Pltp knockout (KO) mice accumulate more free cholesterol and phospholipids than wildtype (WT) controls ( 8 ). On chow diet, Pltp KO/ Apoe KO mice have signifi cantly less atherosclerosis than Apoe KO controls ( 4 ).The role of plasma total cholesterol in atherogenesis has been well established. However, plasma cholesterol exists in two forms: cholesteryl ester and free (unesterifi ed) cholesterol. There is evidence suggesting that free cholesterol plays an important role in atherosclerosis. Free cholesterol has been observed in human atherosclerotic lesions, both intracellularly and extracellularly ( 9 ). Furthermore, free cholesterol accumulates more in severe lesions than in mild ones in the same aorta ( 10 ). In a cell culture model, free Abstract A high saturated fat diet induces free cholesterol and phospholipid accumulation in the plasma of phospholipid transfer protein ( Pltp )-defi cient mice. In this study, we examined the atherogenic consequence of this phenomenon and investigated the possible mechanism(s). Pltp KO/ Apoe KO mice that were fed a coconut oil-enriched high-fat diet (COD) for 7 weeks had higher plasma free cholesterol (149%), phospholipids (15%), and sphingomyelin (54%) than Apoe KO controls. In contrast to chow-fed animals, COD-fed Pltp KO/ Apoe KO mice had the same atherosclerotic lesion size as that of Apoe KO mice. Similar to Pltp KO mice, plasma from COD-fed Pltp KO /Apoe KO mice contained VLDL/ LDL-sized lamellar particles. Bile measurement indicated that COD-fed Pltp KO mice have 33% less hepatic cholesterol output than controls. In conclusion, COD-fed, Pltpdefi cient mice are no longer protected from atherosclerosis and have impaired biliary lipid secretion, which is associated with free cholesterol and phospholipid accumulation. -Yeang, C., S. Qin, K. Chen, D. Q-H. Wang, and X-C. Jiang. Diet-induced lipid accumulation in phospholipid transfer protein-defi cient mice: its atherogenicity and potential mechanism. J. Lipid Res. 2010. 51: 2993-3002.

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Formation of lipoprotein-X. Its relationship to bile compounds.

Cited by 139 publications

References 36 publications

Correctable Plasma Lipoprotein Abnormalities in Infants with Choledochal Cysts

Correctable Plasma Lipoprotein Abnormalities in Infants with Choledochal Cysts

Class III P-glycoproteins mediate the formation of lipoprotein X in the mouse.

Diet-induced lipid accumulation in phospholipid transfer protein-deficient mice: its atherogenicity and potential mechanism

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