Rat Intestine Secretes Discoid High Density Lipoprotein

Green, P. H. R.; Tall, Alan R.; Glickman, Robert M.

doi:10.1172/jci108963

Cited by 252 publications

(85 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10). Early studies involving mesenteric lymph collection (71) and liver perfusion (72) concluded that HDL was produced in these two organs. Tissue-specific knockout experiments will be required to sort out the relative contributions of liver and intestine to HDL production.…”

Section: Discussionmentioning

confidence: 99%

ABCA1 Is Essential for Efficient Basolateral Cholesterol Efflux during the Absorption of Dietary Cholesterol in Chickens

Mulligan

Flowers

Tebon

et al. 2003

Journal of Biological Chemistry

111

View full text Add to dashboard Cite

The ATP-binding cassette transporter A1 (ABCA1) participates in the efflux of cholesterol from cells. It remains unclear whether ABCA1 functions to efflux cholesterol across the basolateral or apical membrane of the intestine. We used a chicken model of ABCA1 dysfunction, the Wisconsin hypoalpha mutant (WHAM) chicken, to address this issue. After an oral gavage of radioactive cholesterol, the percentage appearing in the bloodstream was reduced by 79% in the WHAM chicken along with a 97% reduction in the amount of tracer in high density lipoprotein. In contrast, the percentage of radioactive cholesterol absorbed from the lumen into the intestine was not affected by the ABCA1 mutation. Liver X receptor (LXR) agonists have been inferred to decrease cholesterol absorption through activation of ABCA1 expression. However, the LXR agonist T0901317 decreased cholesterol absorption equally in both wild type and WHAM chickens, indicating that the effect of LXR activation on cholesterol absorption is independent of ABCA1. The ABCA1 mutation resulted in accumulation of radioactive cholesterol ester in the intestine and the liver of the WHAM chicken (5.0-and 4.4-fold, respectively), whereas biliary lipid concentrations were unaltered by the WHAM mutation. In summary, ABCA1 regulates the efflux of cholesterol from the basolateral but not apical membrane in the intestine and the liver.

show abstract

Section: Discussionmentioning

confidence: 99%

ABCA1 Is Essential for Efficient Basolateral Cholesterol Efflux during the Absorption of Dietary Cholesterol in Chickens

Mulligan

Flowers

Tebon

et al. 2003

Journal of Biological Chemistry

111

View full text Add to dashboard Cite

show abstract

“…We and others found that a human intestinal cell line, CaCo-2, expresses ABCA1 ( 9,10 ) and secretes HDL though the involvement of ABCA1 ( 11 ). Experimental studies with rodents have demonstrated that the liver and small intestine (SI) are the major organs for ABCA1 expression and HDL production (12)(13)(14)(15)(16). Recent fi ndings have shown that, although the overexpression of hepatic ABCA1 in experimental mouse models is not benefi cial ( 17 ), the overexpression of intestinal ABCA1 is benefi cial for atherosclerosis ( 18 ), indicating that HDL from SI may perform unique and distinct functions.…”

Section: Western Blot Analysesmentioning

confidence: 99%

“…HDL fractions from mouse serum, SI lymph perfusate, SI lymph ( 14 ), and liver perfusate ( 28 ) from WT mice were buffer exchanged with 10 mM triethylammonium bicarbonate buffer (Sigma-Aldrich, St. Louis, MO) and concentrated by centrifugation (6,000 g , 30 min at 4°C) using Vivaspin2 (MW 3000; GE Healthcare, Buckinghamshire, UK). The protein concentration of each sample was determined with the Bradford method and adjusted to 7.5 mg/ml.…”

Section: Ms Analysis Of Hdl Fractionsmentioning

confidence: 99%

See 1 more Smart Citation

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

Yamaguchi

Zhang

Tomonaga

et al. 2014

Journal of Lipid Research

View full text Add to dashboard Cite

HDL is unquestionably a major antiatherogenic factor worldwide, regardless of sex, race, and age ( 1, 2 ). Therefore, an increase in HDL levels has been an important goal that guides the development of novel therapies for atherosclerotic cardiovascular diseases ( 3 ) because it was reported that plasma HDL cholesterol (HDL-C) levels were reduced in patients with ischemic heart disease and stroke ( 4, 5 ). Strategies for raising HDL are now available. Because remarkable progress has been made in our understanding of the molecular mechanism of HDL production, enhanced production is one of the major strategies for raising HDL.ABCA1, mutations of which are the genetic cause of Tangier disease and genetic HDL defi ciency, is one of the Abstract The small intestine (SI) is the second-greatest source of HDL in mice. However, the selective evaluation of SI-derived HDL (SI-HDL) has been diffi cult because even the origin of HDL obtained in vivo from the intestinal lymph duct of anesthetized rodents is doubtful. To shed light on this question, we have developed a novel in situ perfusion technique using surgically isolated mouse SI, with which the possible fi ltration of plasma HDL into the SI lymph duct can be prevented. With the developed method, we studied the characteristics of and mechanism for the production and regulation of SI-HDL. Nascent HDL particles were detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1 plays an important role in intestinal HDL production, and SI-HDL is small, dense, rich in apo AIV, and regulated by nutritional and genetic factors.

show abstract

“…From this it has been concluded that the discoidal particles are nascent high-density lipoproteins and that these precursor lipoproteins are converted to mature circulating high-density lipoproteins by lecithin -cholesterol acyltransferase. The main apolipoprotein of the discoidal lymph high-density lipoproteins is apolipoprotein A-I [34]. On the contrary, in 'nascent' liver high-density lipoproteins, apolipoprotein-E has been described as the main apolipoprotein [9].…”

Section: Discussionmentioning

confidence: 99%

Substitution in vitro of Lecithin–Cholesterol Acyltransferase

Utermann

Menzel

Adler

et al. 1980

European Journal of Biochemistry

View full text Add to dashboard Cite

Lecithin -cholesterol acyltransferase (EC 2.3.1.43) was purified 15 000-fold from human plasma. The active material was homogeneous in different gel electrophoretic systems but separated into three major bands with apparent pl values of 4.28, 4.33 and 4.37 in isoelectrofocusing. The apparent M , of the enzyme is 67000 f 2000. An antiserum prepared against the purified enzyme specifically inhibited the activity of lecithin -cholesterol acyltransferase in whole serum.Serum from a patient with familial deficiency of lecithin -cholesterol acyltransferase was substituted in vitro with the highly purified enzyme. The serum from this patient did not contain immunochemically detectable enzyme protein. Substitution of enzyme resulted in the following major changes.1. Cholesteryl ester content in serum increased by 36 -89 mg/lOO ml depending on the experimental conditions. The enzyme -mediated formation of cholesteryl ester led to an increase of cholesteryl ester content in high-density and very-low-density lipoproteins and in low-density lipoproteins containing apoprotein-B. No increase occurred in fractions containing very large flattened structures and the abnormal lipoprotein-X and in lipoprotein-E. Incubation of isolated fractions with lecithin -cholesterol acyltransferase led to significant cholesterol esterification only in highdensity lipoproteins.2. The characteristic disc-shaped rouleaux-forming high-density lipoproteins of enzyme-deficient serum disappeared. Instead a single homogeneous population of high-density lipoproteins formed. The particles generated were spherical and had the electrophoretic properties, density (1.080 g/ml), diameter (12.5 nm) and apoprotein composition of normal high-density lipoproteins-2.3. The concentration of spherical particles containing apolipoprotein E (density 1.040-1.080 g/ ml) and the lamellar lipoprotein-X-like structures in the low-density lipoprotein fraction were not affected by the enzyme substitution.4. A single homogeneous population of spherical lipoprotein-B particles of 26.5-nm diameter occurred at density 1.029 g/ml.The data suggest that the discoidal high-density lipoproteins are the major site of cholesteryl ester formation that apolipoprotein-E iq not involved in an undirectional transport of newly formed cholesteryl ester from high-density lipoproteins to other lipoproteins and that lipoprotein-X and lipoprotein-E are not preferential substrates for the acyltransferase.Lecithin -cholesterol acyltransferase is an enzyme present in human serum that catalyses the transfer of a fatty acid residue preferentially from the b-position of phosphatidylcholine to the hydroxyl group of cholesterol [l].Primary deficiency of the acyltransferase is a rare hereditary disorder transmitted as an autosomal reEnzyme. Lecithin -cholesterol acyltransferase (EC 2.3.1.43). cessive trait. Clinically the enzyme deficiency results in anaemia, nephropathia and corneal opacity (for review see [2]). High-density lipoproteins that are considered the main site of acyltransferase catalysed ch...

show abstract

Rat Intestine Secretes Discoid High Density Lipoprotein

Cited by 252 publications

References 26 publications

ABCA1 Is Essential for Efficient Basolateral Cholesterol Efflux during the Absorption of Dietary Cholesterol in Chickens

ABCA1 Is Essential for Efficient Basolateral Cholesterol Efflux during the Absorption of Dietary Cholesterol in Chickens

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

Substitution in vitro of Lecithin–Cholesterol Acyltransferase

Contact Info

Product

Resources

About