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Niacin action in the atherogenic mixed dyslipidemia of metabolic syndrome: Insights from metabolic biomarker profiling and network analysis.
- Source :
-
Journal of clinical lipidology [J Clin Lipidol] 2018 May - Jun; Vol. 12 (3), pp. 810-821.e1. Date of Electronic Publication: 2018 Mar 29. - Publication Year :
- 2018
-
Abstract
- Background: Niacin as an adjunct to statin treatment to reduce cardiovascular risk is questioned.<br />Objective: To evaluate interrelationships between the effects of niacin on mixed dyslipidemia and a spectrum of metabolic and inflammatory biomarkers.<br />Methods: Obese, nondiabetic, hypertriglyceridemic males (n = 19) with low high-density lipoprotein-cholesterol levels received extended-release nicotinic acid for 8 weeks. Multiple biomarkers were measured using enzyme-linked immunosorbent assay, enzymatic/absorptiometric, or multiplex biochip assays. Treatment effects were determined for each variable and a differential correlation network created on the basis of univariate correlations between baseline and response to niacin treatment for all pairs of variables.<br />Results: Extended-release niacin treatment favoured normalization of plasma lipid and apolipoprotein profile. Plasma markers of inflammation, hepatic function, cellular adhesion and proliferation, and macrophage phenotype were attenuated; however, insulin resistance increased. Differential network analysis revealed that changes in triglycerides and high-density lipoprotein-cholesterol were closely linked; equally, niacin mediated reductions in total cholesterol, apolipoprotein B, low-density lipoprotein-cholesterol and lipoprotein(a) clustered together, as did homeostatic model assessment of insulin resistance, insulin, and interleukin-6 levels. Two clusters of inflammatory markers were identified, involving (1) intercellular adhesion molecule 1 and high-sensitive C-reactive protein and (2) soluble tumor necrosis factor receptors; and novel clusters involving matrix metallopeptidase 9 and apolipoprotein E, and adiponectin and cystatin C, respectively, were equally revealed. At lower stringency, lipid and insulin resistance clusters were linked; a C-reactive protein-centered cluster linked reduction in apolipoprotein CIII to intercellular adhesion molecule 1, gamma-glutamyltransferase, soluble tumor necrosis factor receptors, and E-selectin.<br />Conclusion: A niacin-mediated trend to normalize atherogenic mixed dyslipidemia was intimately linked to attenuation of biomarkers of inflammation, cell adhesion, hepatic dysfunction and cell proliferation, but to enhanced insulin resistance and plasma homocysteine elevation.<br /> (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Biomarkers metabolism
Blood Coagulation drug effects
Dyslipidemias metabolism
Dyslipidemias physiopathology
Humans
Insulin Resistance
Liver drug effects
Liver physiopathology
Macrophages drug effects
Male
Middle Aged
Niacin therapeutic use
Phenotype
Dyslipidemias complications
Dyslipidemias drug therapy
Metabolic Syndrome complications
Niacin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1933-2874
- Volume :
- 12
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of clinical lipidology
- Publication Type :
- Academic Journal
- Accession number :
- 29753732
- Full Text :
- https://doi.org/10.1016/j.jacl.2018.03.083