The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice.
The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice.
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DOI：
10.1161/circulationaha.111.067801
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发表时间：
2012-04-10
期刊：
影响因子：
37.8
通讯作者：
Colucci WS
中科院分区：
文献类型：
--
作者：
Qin F;Siwik DA;Luptak I;Hou X;Wang L;Higuchi A;Weisbrod RM;Ouchi N;Tu VH;Calamaras TD;Miller EJ;Verbeuren TJ;Walsh K;Cohen RA;Colucci WS
饮食诱导的肥胖与代谢性心脏病有关，其特征是左心室（LV）肥大和舒张功能障碍。多酚如白藜芦醇（RSV）和合成类黄酮衍生物S17834在各种环境中发挥有益的全身和心血管作用，包括糖尿病和慢性血液动力学超负荷。我们表征了饮食诱导的代谢综合征小鼠模型的结构和功能特征，并使用该模型来检验多酚预防心肌肥大和舒张功能障碍的假设。雄性C57 BL/6 J小鼠喂食正常饮食或高脂肪和高糖饮食（HFHS），伴或不伴S17834或RSV治疗，持续8个月。HFHS饮食喂养的小鼠发生进行性LV肥大和舒张功能障碍，同时保留与肌细胞肥大和间质纤维化相关的收缩功能。在HFHS喂养的小鼠中，心肌氧化应激增加，有证据表明氧化剂介导的蛋白质修饰通过酪氨酸硝化和4-OH-2-壬烯醇（HNE）加合。HFHS喂养的小鼠还表现出血浆空腹葡萄糖、胰岛素和HOMA-IR的增加，表明胰岛素抵抗。S17834或RSV治疗可预防LV肥大和舒张功能障碍。对于S17834，这些有益作用与氧化剂介导的蛋白质修饰和高胰岛素血症减少以及血浆脂联素增加相关。RSV和S17834与HFHS饮食同时给药可预防LV肥大、间质纤维化和舒张功能障碍的发生。多种机制可能有助于多酚的有益作用，包括减少心肌氧化应激和相关蛋白质修饰，改善胰岛素抵抗和增加血浆脂联素。多酚RSV和S17834可能在预防饮食诱导的代谢性心脏病中具有价值。
Diet-induced obesity is associated with metabolic heart disease characterized by left ventricular (LV) hypertrophy and diastolic dysfunction. Polyphenols such as resveratrol (RSV) and the synthetic flavonoid derivative S17834 exert beneficial systemic and cardiovascular effects in a variety of settings including diabetes and chronic hemodynamic overload. We characterized the structural and functional features of a mouse model of diet-induced metabolic syndrome, and used the model to test the hypothesis that the polyphenols prevent myocardial hypertrophy and diastolic dysfunction. Male C57BL/6J mice were fed a normal diet or a diet high in fat and sugar (HFHS) with or without concomitant treatment with S17834 or RSV for up to 8 months. HFHS diet-fed mice developed progressive LV hypertrophy and diastolic dysfunction with preservation of systolic function in association with myocyte hypertrophy and interstitial fibrosis. In HFHS-fed mice there was increased myocardial oxidative stress with evidence of oxidant-mediated protein modification via tyrosine nitration and 4-OH-2-nonenol (HNE) adduction. HFHS-fed mice also exhibited increases in plasma fasting glucose, insulin and HOMA-IR indicative of insulin resistance. Treatment with S17834 or RSV prevented LV hypertrophy and diastolic dysfunction. For S17834, these beneficial effects were associated with decreases in oxidant-mediated protein modifications and hyper-insulinemia, and increased plasma adiponectin. RSV and S17834 administered concurrently with a HFHS diet prevent the development of LV hypertrophy, interstitial fibrosis and diastolic dysfunction. Multiple mechanisms may contribute to the beneficial effects of the polyphenols including a reduction in myocardial oxidative stress and related protein modifications, amelioration of insulin resistance and increased plasma adiponectin. The polyphenols RSV and S17834 may be of value in the prevention of diet-induced metabolic heart disease.