Vitamin B3 impairs reverse cholesterol transport in Apolipoprotein E-deficient mice
Clin Investig Arterioscler. 2019 Nov-Dec;31(6):251-260.
doi: 10.1016/j.arteri.2019.04.001.
Epub 2019 May 13.
[Article in
English,
Spanish]
Affiliations
- 1 Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau i Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: kmendez@santpau.cat.
- 2 CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain.
- 3 Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
- 4 Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain; Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
- 5 Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau i Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
- 6 CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain; Servei d'Endocrinologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
- 7 Servei d'Endocrinologia, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
- 8 Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau i Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 9 CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain; Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
- 10 Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau i Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jjulve@santpau.cat.
Abstract
Introduction:
High Density Lipoproteins (HDL) are dysfunctional in hypercholesterolemia patients. The hypothesis was tested that nicotinamide (NAM) administration will influence HDL metabolism and reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT) in a murine model of hypercholesterolemia.
Methods:
Apolipoprotein E-deficient (KOE) mice were challenged with a high-fat diet for 4 weeks. The effect of different doses of NAM on cholesterol metabolism, and the ability of HDL to promote m-RCT was assessed.
Results:
The administration of NAM to KOE mice produced an increase (∼1.5-fold; P<0.05) in the plasma levels of cholesterol, which was mainly accounted for by the non-HDL fraction. NAM produced a [3H]-cholesterol plasma accumulation (∼1.5-fold) in the m-RCT setting. As revealed by kinetic analysis, the latter was mainly explained by an impaired clearance of circulating non-HDL (∼0.8-fold). The relative content of [3H]-tracer was lowered in the livers (∼0.6-fold) and feces (>0.5-fold) of NAM-treated mice. This finding was accompanied by a significant (or trend close to significance) up-regulation of the relative gene expression of Abcg5 and Abcg8 in the liver (Abcg5: 2.9-fold; P<0.05; Abcg8: 2.4-fold; P=0.06) and small intestine (Abcg5: 2.1-fold; P=0.15; Abcg8: 1.9-fold; P<0.05) of high-dose, NAM-treated mice.
Conclusion:
The data from this study show that the administration of NAM to KOE mice impaired m-RCT in vivo. This finding was partly due to a defective hepatic clearance of plasma non-HDL.
Keywords:
Arteriosclerosis; Atherosclerosis; Función de HDL; HDL function; Hipercolesterolemia; Hypercholesterolemia.
Copyright © 2019 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
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ATP Binding Cassette Transporter, Subfamily G, Member 8 / genetics
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Animals
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Apolipoproteins E / deficiency*
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Biological Transport / drug effects
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Cholesterol / blood
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Cholesterol / metabolism*
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Diet, High-Fat
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Feces
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Gene Expression
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Hypercholesterolemia / metabolism*
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Lipoproteins / genetics
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Lipoproteins, HDL
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Liver / metabolism*
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Macrophages / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Niacinamide / administration & dosage*
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Reverse Transcriptase Polymerase Chain Reaction
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Up-Regulation
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Vitamin B Complex / administration & dosage*
Substances
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ABCG5 protein, mouse
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ABCG8 protein, mouse
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ATP Binding Cassette Transporter, Subfamily G, Member 5
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ATP Binding Cassette Transporter, Subfamily G, Member 8
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Apolipoproteins E
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Lipoproteins
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Lipoproteins, HDL
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Vitamin B Complex
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Niacinamide
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Cholesterol