Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats

Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats
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DOI:
10.1016/j.nutres.2015.02.008
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发表时间:
2015-04-01
期刊:
影响因子:
4.5
通讯作者:
Blade, Cinta
Blade, Cinta
中科院分区:
医学3区
文献类型:
--
作者:
Baselga-Escudero, Laura;Pascual-Serrano, Aida;Blade, Cinta

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miR-33和miR-122作为肝脏脂质代谢的主要调节因子,其失调与肥胖和代谢综合征有关。原花青素在健康动物中抑制这些microRNA。因此,我们假设长期食用膳食原花青素可以使miR-33 a和miR-122的表达正常化。因此,本研究的目的是确定长期食用原花青素是否可以有效地使高脂饮食导致肥胖的大鼠的miR-33 a和miR-122的表达正常化,并确定有效剂量。大鼠维持在高脂肪饮食,有或没有补充葡萄籽原花青素提取物在低,中,或高剂量的人消费。结果显示,对于所有研究剂量,补充葡萄籽原花青素提取物3周使肥胖大鼠肝脏中miR-33 a和miR-122的过表达正常化,没有剂量依赖性结果,并且还以剂量依赖性方式降低血浆和肝脏脂质水平。总之,低持续剂量的原花青素,低于欧洲人群的估计平均摄入量,足以使肥胖大鼠肝脏中的miR-33 a和miR-122水平正常化。因此,肥胖期间富含原花青素的饮食至少在分子水平上可以改善某些代谢综合征症状。(C)2015 Elsevier Inc. All rights reserved.
Deregulation of miR-33 and miR-122, as major regulators of lipid metabolism in liver, has been related to obesity and metabolic syndrome. Proanthocyanidins repress these microRNAs in healthy animals. Hence, we hypothesized that long-term consumption of dietary proanthocyanidins can normalize the expression of miR-33a and miR-122. Therefore, the objective of this work was to determine whether the long-term consumption of proanthocyanidins could effectively normalize the expression of miR-33a and miR-122 in rats made obese by a high-fat diet and to determine the effective dose. Rats were maintained on the high-fat diet with or without supplementation with a grape seed pro anthocyanidin extract at low, medium, or high dose in relation to human consumption. Results show that 3 weeks of supplementation with grape seed proanthocyanidin extract normalized the overexpression of miR-33a and miR-122 in obese rats' liver for all doses studied, with no dose-dependent outcome, and also reduced the levels of plasma and liver lipids in a dose-dependent manner. In conclusion, a low sustained dose of proanthocyanidins, lower than the estimated mean intake for a European population, is enough to normalize miR-33a and miR-122 levels in the livers of obese rats. Therefore, a proanthocyanidin-rich diet during obesity can improve some of the metabolic syndrome symptoms at least at the molecular level. (C) 2015 Elsevier Inc. All rights reserved.