The Role of Serum Free Fatty Acids in Endothelium-Dependent Microvascular Function

IF 2.7 Q3 ENDOCRINOLOGY & METABOLISM
Alexander E. Sullivan, Meaghan C. S. Courvan, Aaron W. Aday, David H. Wasserman, Kevin D. Niswender, Emily M. Shardelow, Emily K. Wells, Quinn S. Wells, Matthew S. Freiberg, Joshua A. Beckman
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引用次数: 0

Abstract

Background

Elevated serum free fatty acid (FFA) concentration is associated with insulin resistance and is a hallmark of metabolic syndrome. A pathological feature of insulin resistance is impaired endothelial function.

Objective

To investigate the effect of FFA reduction with either acipimox, a nicotinic acid derivative that impairs lipolysis, or salsalate, a salicylate that reduces basal and inflammation-induced lipolysis, on insulin-mediated endothelium-dependent vasodilation.

Methods

This was a post hoc, combined analysis of two randomised, double-blind, placebo-controlled crossover trials. Sixteen subjects were recruited (6 with metabolic syndrome and 10 controls) and randomised to acipimox 250 mg orally every 6 h for 7 days or placebo. Nineteen subjects were recruited (13 with metabolic syndrome and 6 controls) and randomised to receive salsalate 4.5 g/day for 4 weeks or placebo. The primary outcome was the association between FFA concentration and insulin-mediated vasodilation, measured by venous-occlusion strain-gauge plethysmography at baseline and following FFA modulation with the study drugs.

Results

At baseline, FFA concentration (R = −0.35, p = 0.043) and insulin sensitivity (HOMA-IR: R = −0.42, p = 0.016, Adipo-IR: R = −0.39, p = 0.025) predicted insulin-mediated vasodilation. FFA levels were significantly reduced after drug pretreatment (0.604 vs. 0.491 mmol/L, p = 0.036) while insulin levels, insulin sensitivity and inflammatory markers were unchanged. Despite a reduction in circulating FFA with drug therapy, neither insulin-stimulated vasodilation nor insulin sensitivity improved.

Conclusions

Short-term reduction of FFA concentration does not improve insulin-stimulated vasodilation in patients with metabolic syndrome.

Trial Registration

ClinicalTrials.gov identifier: NCT00759291 and NCT00760019 (formerly NCT00762827)

Abstract Image

血清游离脂肪酸在内皮依赖性微血管功能中的作用。
背景:血清游离脂肪酸(FFA)浓度升高与胰岛素抵抗有关,是代谢综合征的标志。胰岛素抵抗的一个病理特征是内皮功能受损。目的:研究阿昔莫克斯(一种损害脂肪分解的烟酸衍生物)或水杨酸盐(一种减少基础和炎症诱导的脂肪分解的水杨酸盐)对胰岛素介导的内皮依赖性血管舒张的影响。方法:这是一项对两个随机、双盲、安慰剂对照交叉试验的事后联合分析。招募了16名受试者(6名代谢综合征患者和10名对照组),随机分配到每6小时口服250mg阿昔莫克斯,连续7天或安慰剂组。招募了19名受试者(13名代谢综合征患者和6名对照组),随机分为每天服用4.5 g水杨酸盐,持续4周或安慰剂。主要结果是FFA浓度与胰岛素介导的血管舒张之间的关系,通过静脉阻塞应变计容积描画在基线和使用研究药物调节FFA后测量。结果:基线时,FFA浓度(R = -0.35, p = 0.043)和胰岛素敏感性(HOMA-IR: R = -0.42, p = 0.016, Adipo-IR: R = -0.39, p = 0.025)预测胰岛素介导的血管舒张。药物预处理后患者FFA水平显著降低(0.604 vs. 0.491 mmol/L, p = 0.036),而胰岛素水平、胰岛素敏感性和炎症标志物无变化。尽管药物治疗降低了循环FFA,但胰岛素刺激的血管舒张和胰岛素敏感性都没有改善。结论:短期降低FFA浓度并不能改善代谢综合征患者胰岛素刺激的血管舒张。试验注册:ClinicalTrials.gov标识符:NCT00759291和NCT00760019(原NCT00762827)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Endocrinology, Diabetes and Metabolism
Endocrinology, Diabetes and Metabolism Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.00
自引率
0.00%
发文量
66
审稿时长
6 weeks
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