Diets deficient in selenium and vitamin E affect plasma lipoprotein and apolipoprotein concentrations in the rat

The present study examined the effects of Se, vitamin E and combined Se and vitamin E deficiencies in rats on plasma lipid, Lipoprotein and apolipoprotein (apo) concentrations. Deficiencies were induced by feeding rats the respective diets for 6 weeks. The study shows that Se deficiency results in increased concentrations of plasma cholesterol and apo E. Both could be explained by an increase in the HDL1 fraction. Vitamin E deficiency alone had no significant effect on plasma lipid, lipoprotein and apo concentrations. Se deficiency in combination with vitamin E deficiency leads to an increase in plasma LDL and apo B concentrations. These results point to the need for further investigations on the mechanism by which Se deficiency affects lipoprotein metabolism.

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Hypertriglyceridemia and Lower LDL Cholesterol Concentration in Relation to Apolipoprotein E Phenotypes in Myotonic Dystrophy

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100028675 ◽

1989 ◽

Vol 16 (1) ◽

pp. 129-133 ◽

Cited By ~ 8

Author(s):

Sital Moorjani ◽

Daniel Gaudet ◽

Claude Laberge ◽

Marie Christine Thibault ◽

Jean Mathieu ◽

...

Keyword(s):

Myotonic Dystrophy ◽

Ldl Cholesterol ◽

Plasma Cholesterol ◽

Plasma Lipid ◽

Cholesterol Concentration ◽

Plasma Triglycerides ◽

Ldl Particles ◽

Vldl Cholesterol ◽

Apo E

ABSTRACT:Plasma lipid, lipoprotein levels and apolipoprotein apo E phenotypes were determined in 70 patients with myotonic dystrophy (MyD) and 81 controls. Marked differences were noticed in the apo E phenotype frequencies between the two groups. Plasma triglycerides and VLDL cholesterol were higher in MyD than controls, but only the latter was related to differences in the apo E phenotypes between two groups. Accordingly, the ratio of VLDL cholesterol/plasma triglycerides was increased significantly in MyD, suggesting accumulation of intermediary density particles due to lower affinity of E2 containing lipoproteins for lipoprotein cell receptors. The LDL cholesterol concentration was lower in MyD than controls and was related to differences in the apo E phenotype frequencies between the two groups. These results indicate increased removal of LDL particles in the apo E2 phenotypes, perhaps due to upregulation of LDL (B, E) receptor activity. Plasma cholesterol and HDL cholesterol concentrations were similar in both groups. Another feature of the study was lower levels of plasma cholesterol, triglycerides, VLDL and LDL cholesterol in the homozygous E4:E4 phenotype. These results suggest increased clearance rate of both VLDL and LDL particles and support the concept that apo E4-containing lipoproteins have higher in vivo affinity for ape E and/or B, E receptors.

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ILRUN , a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice

Circulation Research ◽

10.1161/circresaha.120.317175 ◽

2020 ◽

Vol 127 (11) ◽

pp. 1347-1361 ◽

Cited By ~ 1

Author(s):

Xin Bi ◽

Takashi Kuwano ◽

Paul C. Lee ◽

John S. Millar ◽

Li Li ◽

...

Keyword(s):

Plasma Lipids ◽

Plasma Cholesterol ◽

Plasma Lipid ◽

Lipoprotein Metabolism ◽

Peroxisome Proliferator ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Peroxisome Proliferator Activated Receptor ◽

Liver Transcriptome ◽

Artery Disease

Rationale: Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated–like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. Objective: To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. Methods and Results: ILRUN encodes a protein that contains a ubiquitin-associated–like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun -deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated–like domain of ILRUN was found to be required for its interaction with PPARα. Conclusions: These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.

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Altered lipoprotein metabolism in spontaneous vitamin E deficiency of owl monkeys

American Journal of Clinical Nutrition ◽

10.1093/ajcn/38.6.888 ◽

1983 ◽

Vol 38 (6) ◽

pp. 888-894 ◽

Cited By ~ 7

Author(s):

S N Meydani ◽

R J Nicolosi ◽

P K Sehgal ◽

K C Hayes

Keyword(s):

Vitamin E ◽

Lipoprotein Metabolism ◽

Vitamin E Deficiency ◽

Owl Monkeys

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Supplementation with Vitamin E and/or Zinc does not Attenuate Atherosclerosis in Apolipoprotein E-deficient Mice fed a High-Fat, High-Cholesterol Diet

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.71.1.45 ◽

2001 ◽

Vol 71 (1) ◽

pp. 45-52 ◽

Cited By ~ 19

Author(s):

Antoni Paul ◽

Luía Calleja ◽

Jorge Joven ◽

Elisabet Vilella ◽

Natàlia Ferré ◽

...

Keyword(s):

Vitamin E ◽

Plasma Cholesterol ◽

Plasma Concentrations ◽

Water Soluble ◽

High Cholesterol Diet ◽

Hypolipidemic Effect ◽

Sod Activity ◽

Apo E ◽

Oxidative Processes ◽

Deficient Mice

Ever since oxidation has been known to be involved in atherogenesis, antioxidants have received considerable attention as potential antiatherogenic agents. The lipid-soluble vitamin E is the main antioxidant carried by lipoproteins. Zinc is a water-soluble trace element that acts as a cofactor of superoxide dismutase (SOD) and has an antioxidant role in several oxidative processes. To test the hypothesis that zinc could adjuvate the antioxidant activity of vitamin E and diminish atherogenesis, we explored how supplementing diet with vitamin E and/or zinc would affect an atherosclerosis-prone animal like Apo E-deficient mice. The increased plasma concentrations of both vitamin E and zinc showed that absorption was high. They had a significant hypolipidemic effect and the supplemented animals had 25% less plasma cholesterol and triglyceride than controls. The SOD activity was significantly higher in washed erythrocytes from mice supplemented with zinc. The plasma of supplemented animals was also significantly more resistant to oxidation. The size of lesions in the proximal aortic region did not differ among groups. Therefore, dietary supplementation resulted in the expected antioxidant effects but there was no substantial attenuation of atherosclerosis in this particular model.

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Lipoprotein metabolism

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.1233 ◽

2011 ◽

pp. 1659-1667 ◽

Cited By ~ 1

Author(s):

Bo Angelin ◽

Paolo Parini

Keyword(s):

Fatty Acids ◽

Lipid Metabolism ◽

Plasma Lipids ◽

Plasma Lipid ◽

Lipoprotein Metabolism ◽

Protective Role ◽

Plasma Lipoprotein ◽

Major Function ◽

Signalling Molecules ◽

Genetic And Environmental Factors

The realization that raised concentrations of plasma lipids, particularly cholesterol, are associated with an increased risk of coronary heart disease has stimulated the study of factors regulating plasma lipid metabolism. With the use of increasingly refined methodology, our understanding of normal plasma lipoprotein metabolism and its derangements due to the influence of genetic and environmental factors is continuously expanding. This chapter summarizes some current concepts regarding plasma lipoprotein transport in normal humans, forming a basis for the discussion of the development of various dyslipidaemias in the following chapters. Lipids represent a heterogeneous group of substances with several biological functions. Phospholipids and cholesterol are essential components of cell membranes, and cholesterol is also the precursor of steroid hormones and bile acids. Some fatty acids form the origin of bioactive compounds such as prostaglandins, thromboxanes, and leukotrienes; phospholipids, fatty acids, and cholesterol may also serve as signalling molecules in their own right. Furthermore, lipid complexes are necessary for the transport of lipid-soluble vitamins, and may have a protective role in the defence against toxins and infectious agents. From an overall physiological perspective, however, the major function of plasma lipid metabolism is the exchange of fat as energy substrates.

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A comparison of the effect of genetic variation in the genes for apo B & apo E in the determination of normal plasma lipid lipoprotein concentrations

Atherosclerosis ◽

10.1016/0021-9150(87)90219-x ◽

1987 ◽

Vol 68 (3) ◽

pp. 274

Author(s):

R.S. Houlston ◽

J.L. Hutson ◽

D. Hassall ◽

P. Talmud ◽

B. Lewis ◽

...

Keyword(s):

Genetic Variation ◽

Plasma Lipid ◽

Apo B ◽

Normal Plasma ◽

Apo E

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Assessment of Tocopherol Metabolism and Oxidative Stress in Familial Hypobetalipoproteinemia

Clinical Chemistry ◽

10.1373/clinchem.2006.068692 ◽

2006 ◽

Vol 52 (7) ◽

pp. 1339-1345 ◽

Cited By ~ 22

Author(s):

Michael W Clarke ◽

Amanda J Hooper ◽

Henrietta A Headlam ◽

Jason HY Wu ◽

Kevin D Croft ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Ldl Cholesterol ◽

Plasma Concentrations ◽

Lipoprotein Metabolism ◽

Gas Chromatography Mass Spectrometry ◽

Apo B ◽

Familial Hypobetalipoproteinemia ◽

And Oxidative Stress ◽

Vitamin E Supplementation

Abstract Background: Vitamin E supplementation has been recommended for persons with familial hypobetalipoproteinemia (FHBL), a rare disorder of lipoprotein metabolism that leads to low serum α-tocopherol and decreased LDL-cholesterol and apolipoprotein (apo) B. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with FHBL. Methods: We studied 9 individuals with heterozygous FHBL [mean (SE) age, 40 (5) years; body mass index (BMI), 27 (10) kg/m2] and 7 normolipidemic controls [age, 41 (5) years; BMI, 25 (2) kg/m2]. We also studied 3 children—2 with homozygous FHBL (apoB-30.9) and 1 with abetalipoproteinemia—who were receiving α-tocopherol supplementation. We used HPLC with electrochemical detection to measure α- and γ-tocopherol in serum, erythrocytes, and platelets, and gas chromatography–mass spectrometry to measure F2-isoprostanes and tocopherol metabolites in urine as markers of oxidative stress and tocopherol intake, respectively. Results: Compared with controls, persons with FHBL had significantly lower fasting plasma concentrations of total cholesterol [2.4 (0.2) vs 4.7 (0.2) mmol/L], triglycerides [0.5 (0.1) vs 0.9 (0.1) mmol/L], LDL-cholesterol [0.7 (0.1) vs 2.8 (0.3) mmol/L], apoB [0.23 (0.02) vs 0.84 (0.08) g/L], α-tocopherol [13.6 (1.0) vs 28.7 (1.4) μmol/L], and γ-tocopherol [1.0 (0.1) vs 1.8 (0.3) μmol/L] (all P <0.03). Erythrocyte α-tocopherol was decreased [5.0 (0.2) vs 6.0 (0.3) μmol/L; P <0.005], but we observed no differences in lipid-adjusted serum tocopherols, erythrocyte γ-tocopherol, platelet α- or γ-tocopherol, urinary F2-isoprostanes, or tocopherol metabolites. Conclusion: Taken together, our findings do not support the recommendation that persons with heterozygous FHBL receive vitamin E supplementation.

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Receptor interactions controlling lipoprotein metabolism

Canadian Journal of Biochemistry and Cell Biology ◽

10.1139/o85-111 ◽

1985 ◽

Vol 63 (8) ◽

pp. 898-905 ◽

Cited By ~ 3

Author(s):

Karl H. Weisgraber ◽

Thomas L. Innerarity ◽

Stanley C. Rall Jr. ◽

Robert W. Mahley

Keyword(s):

Receptor Binding ◽

Cholesterol Metabolism ◽

Ldl Receptor ◽

Lipoprotein Metabolism ◽

Binding Domain ◽

Cholesterol Homeostasis ◽

Lipoprotein Receptor ◽

Receptor Binding Domain ◽

Apo B ◽

Apo E

Lipoprotein receptors play a central role in lipoprotein metabolism and a major role in cholesterol homeostasis. The most completely characterized lipoprotein receptor is the LDL (low density lipoprotein) or apo-B,E(LDL) receptor. The apo-B,E(LDL) receptor is present on both hepatic and extrahepatic cells and is responsible for the metabolism of a major portion of plasma LDL. Binding and internalization of LDL particles by this receptor initiates a series of intracellular events, resulting in the regulation of cellular cholesterol metabolism. In addition to the apo-B on LDL interacting with the apo-B,E(LDL) receptor, the apo-E on apo-E-containing lipoproteins is also capable of interacting and regulating intracellular cholesterol metabolism. The liver has also been shown to contain a second distinct lipoprotein receptor that is specific for apo-E. This receptor has been demonstrated on hepatic membranes from humans, dogs, and swine and is referred to as the apo-E receptor. This receptor may be responsible for the clearance of chylomicron remnants from plasma by the liver and may participate in reverse cholesterol transport. Thus, apo-E is a major determinant in lipoprotein metabolism and cholesterol homeostasis. The receptor binding properties of apo-E are well characterized, and a series of structural variants, several with lipoprotein binding defects, have been identified. Studies of the binding activity of these receptor-defective apo-E variants have helped to define the receptor binding domain of apo-E. These results, in conjunction with receptor binding studies with various apo-E fragments and with an apo-E monoclonal antibody that inhibits receptor binding, have demonstrated that the receptor binding domain is located in the center of the molecule between residues 140 and 160.

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Stimulation of apolipoprotein secretion in very-low-density and high-density lipoproteins from cultured rat hepatocytes by dexamethasone

Biochemical Journal ◽

10.1042/bj2710575 ◽

1990 ◽

Vol 271 (3) ◽

pp. 575-583 ◽

Cited By ~ 42

Author(s):

P Martin-Sanz ◽

J E Vance ◽

D N Brindley

Keyword(s):

Low Density Lipoprotein ◽

Lipoprotein Metabolism ◽

Density Lipoprotein ◽

Rat Hepatocytes ◽

High Density ◽

High Density Lipoproteins ◽

Low Density ◽

Apo B ◽

Apo E ◽

The Masses

The effects of dexamethasone (a synthetic glucocorticoid) and insulin on the secretion of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) were investigated. Rat hepatocytes in monolayer culture were preincubated for 15 h in the presence or absence of combinations of 100 nM-dexamethasone and 2 nM-, 10 nM- or 50 nM-insulin. Dexamethasone increased [3H]oleate incorporation into secreted triacylglycerol by 2.7-fold and the mass of triacylglycerol secreted by 1.5-fold. Insulin alone decreased these parameters and antagonized the effect of dexamethasone. Dexamethasone increased the secretion of [3H]leucine in apolipoprotein (apo) E, and in the large (BH) and small (BI) forms of apo B in VLDL by about 7.1-, 3.6- and 4.0-fold respectively. Insulin alone decreased the secretion of these 3H-labelled apolipoproteins in VLDL. However, 2 nM-insulin with dexamethasone increased the secretion of 3H-labelled apo BH and apo BL by a further 0.8- and 3.2-fold respectively; 50 nM-insulin decreased the secretions of apo E, apo BH and apo BL in VLDL. Similar effects for dexamethasone or insulin alone were also obtained for the masses of apo E and apo BL + H secreted in VLDL. Albumin secretion was not significantly altered by either dexamethasone or insulin alone, but in combination they stimulated by 2.1-2.6-fold. Insulin or dexamethasone alone had little effect on the secretion of apolipoproteins in the HDL fraction. However, dexamethasone plus 2 nM-insulin increased the incorporation of [3H]leucine into apo AI, apo AH plus apo C, apo AIV and apo E of HDL by about 1.8-, 1.6-, 1.7- and 2.0-fold respectively. The apo E in the bottom fraction represented about 69% of the total 3H-labelled apo E secreted. The responses in the total secretion of apo E from the hepatocytes resembled those seen in HDL. The interactions of insulin and dexamethasone are discussed in relation to the general regulation of lipoprotein metabolism, the development of hyperlipidaemias and the predisposition to premature atherosclerosis.

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