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Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial.

ABSTRACT: OBJECTIVE:Insulin resistance is associated with increased lipolysis and elevated concentrations of free fatty acids (FFA), which in turn contribute to impaired vascular function. It was hypothesized that lowering FFA with acipimox, a nicotinic acid derivative that impairs FFA efflux, would improve endothelial function, measured by flow-mediated dilation (FMD), in individuals with metabolic syndrome. METHODS:A total of 18 participants with metabolic syndrome and 17 healthy controls were enrolled and treated with acipimox 250 mg orally every 6 hours or placebo for 7 days in a randomized, double-blind, crossover trial. RESULTS:Acipimox reduced FFA concentrations among individuals with metabolic syndrome to near normal levels (P = 0.01), but there was no change among healthy controls (P = 0.17). Acipimox did not improve endothelial-dependent FMD in either group (metabolic syndrome: P?=?0.42; healthy controls: P?=?0.16), although endothelial-independent nitroglycerin-mediated dilation among those with metabolic syndrome tended to increase (20.3%, P?=?0.06). There were no changes in blood lipids or markers of inflammation following therapy. There was minimal correlation between change in FMD and baseline measures of BMI (???=?-0.09) or waist circumference (???=?-0.15). CONCLUSIONS:In groups with normal or elevated baseline FFA, short-term reductions do not improve endothelial function assessed by FMD.

SUBMITTER: Aday AW

PROVIDER: S-EPMC6832806 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial.

Aday Aaron W AW Goldfine Allison B AB Gregory Justin M JM Beckman Joshua A JA

Obesity (Silver Spring, Md.) 20191001 11

<h4>Objective</h4>Insulin resistance is associated with increased lipolysis and elevated concentrations of free fatty acids (FFA), which in turn contribute to impaired vascular function. It was hypothesized that lowering FFA with acipimox, a nicotinic acid derivative that impairs FFA efflux, would improve endothelial function, measured by flow-mediated dilation (FMD), in individuals with metabolic syndrome.<h4>Methods</h4>A total of 18 participants with metabolic syndrome and 17 healthy controls ...[more]

PMID: 31571412

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Project description:Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n?=?11) or n-3 PUFA (?-3, n?=?11) supplementation. Before (pre) and after (post) 16?weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ?-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p?=?0.06, ES?=?0.9; and +23 vs. -22%, p?=?0.02, ES?=?1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p?>?0.05). In addition, ?-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p?=?0.04, ES?=?-0.9) and tumor necrosis factor (-13 vs. +0.3%, p?=?0.04, ES?=?-0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p?=?0.1, ES?=?-0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16?weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.

Dataset Information

Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial.

Publications

Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial.

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