Vitamin B3 impairs reverse cholesterol transport in Apolipoprotein E-deficient mice

Karen Alejandra Méndez-Lara, David Santos, Núria Farré, Madalina Nicoleta Nan, Víctor Pallarès, Antonio Pérez-Pérez, Núria Alonso, Joan Carles Escolà-Gil, Francisco Blanco-Vaca, Josep Julve

Research output: Contribution to journalArticleResearch

Abstract

© 2019 Sociedad Española de Arteriosclerosis 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 [ 3 H]-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 [ 3 H]-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.
Original languageEnglish
JournalClinica e Investigacion en Arteriosclerosis
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Atherosclerosis
  • HDL function
  • Hypercholesterolemia

Fingerprint Dive into the research topics of 'Vitamin B3 impairs reverse cholesterol transport in Apolipoprotein E-deficient mice'. Together they form a unique fingerprint.

Cite this