Lower cardiovagal tone and baroreflex sensitivity associated with hepatic insulin resistance and promote cardiovascular disorders in Tibetan minipigs induced by a high fat and high cholesterol diet
Lower cardiovagal tone and baroreflex sensitivity associated with hepatic insulin resistance and promote cardiovascular disorders in Tibetan minipigs induced by a high fat and high cholesterol diet
复制标题
降低与肝胰岛素抵抗相关的心迷走神经张力和压力反射敏感性，并促进高脂肪和高胆固醇饮食诱发的西藏小型猪心血管疾病
DOI：
10.1016/j.jdiacomp.2018.12.014
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发表时间：
2019-04-01
影响因子：
3
通讯作者：
Chen, Minli
中科院分区：
文献类型：
--
作者：
Pan, Yongming;Rong, Yili;Chen, Minli
目的：长期高脂肪/胆固醇（HFC）饮食会导致肝脏胰岛素抵抗（IR），这与自主神经功能障碍和心血管疾病风险增加有关。然而，这种情况是否发生在西藏小型猪身上仍然未知。我们测试发现，长期的 HFC 饮食会导致西藏小型猪的肝脏 IR 并促进心血管疾病，并与心迷走神经张力和压力反射敏感性 (BRS) 的降低有关。 方法：给雄性西藏小型猪饲喂标准饮食或 HFC 饮食，并在 12 周时实施安乐死。此后，对小型猪进行生化血液指数、葡萄糖耐量、血压、心率变异性（HRV）、BRS、胰岛素受体底物（IRS）相关基因和蛋白表达水平以及心脏功能的检测。结果：HFC饲喂的小型猪通过增加体重、总胆固醇、空腹血糖和胰岛素水平、非酯化脂肪酸（NEFA）和高敏C反应蛋白（hs-CRP）水平、葡萄糖耐受不良而出现IR。增加脂肪细胞大小、肝脂肪沉积、丙二醛 (MDA) 含量和 NEFA 水平，IRS1、IRS2、PI3K、Akt、p-Akt、Glut2 和 PGC1 α 表达下调，同时肝组织中 mTOR、GSK3 β、TNF-α、FOXO1、p-mTOR 和 p-p70S6K 表达上调，以及高血压和在饲喂 HFC 的小型猪中观察到左心室舒张功能障碍。 HRV参数和BRS值进一步显着降低。此外，多元线性回归分析表明，肝脏IR向心血管疾病的发展与低HFnu、RMSSD、BRS和LV-dp/dtmax、高NEFA、高肝脏TG含量相关。结论：这些数据表明，HFC喂养的西藏小型猪出现肝脏IR并促进心血管疾病，并与较低的心迷走神经张力和BRS相关。 (C) 2018 Elsevier Inc. 保留所有权利。
Aims: A long-term high-fat/cholesterol (HFC) diet leads to hepatic insulin resistance (IR), which is associated with autonomic dysfunction and cardiovascular diseases risk increasing. However, whether this occurs in Tibetan minipigs remains unknown. We tested that a long-term HFC diet caused hepatic IR and promote cardiovascular disorders in Tibetan minipigs, and are associated with the reduction of cardiovagal tone and baroreflex sensitivity (BRS).Methods: Male Tibetan minipigs were fed either a standard diet or a HFC diet, and were euthanized at 12 weeks. Thereafter, the minipigs were tested for biochemical blood indices, glucose tolerance, blood pressure, heart rate variability (HRV), BRS, and insulin receptor substrate (IRS)-associated gene and protein expression levels, as well as cardiac function.Results: HFC-fed minipigs developed IR by increasing body weight, total cholesterol, fasting blood glucose and insulin levels, and nonesterified fatty acid (NEFA) and high sensitive C-reactive protein (hs-CRP) levels, glucose intolerance. Increased adipose cell size, hepatic fat deposition, malondialdehyde (MDA) content and NEFA level, down-regulation of IRS1, IRS2, PI3K, Akt, p-Akt, Glut2 and PGC1 alpha expression concomitant with up-regulation of mTOR, GSK3 beta, TNF-alpha, FOXO1, p-mTOR and p-p70S6K expression in the liver tissue, as well as hypertension and left ventricular diastolic dysfunction were observed in HFC-fed minipigs. HRV parameters and BRS values were further significantly reduced. Furthermore, multiple linear regression analysis showed that the development of hepatic IR toward cardiovascular disease was associated with low HFnu, RMSSD, BRS and LV - dp/dtmax, high NEFA, high hepatic TG content.Conclusion: These data suggest that HFC-fed Tibetan minipigs develop hepatic IR and promote cardiovascular disorders, and are associated with lower cardiovagal tone and BRS. (C) 2018 Elsevier Inc. All rights reserved.