High fat diet (HFD)-induced obesity adversely affects cardiac outcomes; however the effect of HFD consumption on myocardial remodeling and the underlying mechanisms are still elusive. This study aimed to examine the histological and molecular changes in cardiac tissue of HFD-fed rats. Eight-week old male Wistar rats were fed either HFD or normal chow diet for 16 weeks and then assessed for changes in metabolic and cardiac homeostasis (n = 10 each group). 16 weeks on HFD resulted in obesity, dyslipidemia and altered glucose tolerance but no hypertension. Histological examination of Masson's trichrome stained-cardiac sections revealed massive fibrotic changes, while immunoblotting analysis showed higher expressions of collagens I and III, and fibronectin in cardiac tissue of HFD-fed rats. The expressions of transforming growth factor beta1 and the phosphorylation of its downstream target, Smad3, were significantly increased in cardiac tissue of HFD-fed rats. Activation of endothelial-mesenchymal transition was promoted in hearts of HFD-fed rats, as evidenced by down-regulation of platelet endothelial cell adhesion molecule-1, while upregulation of α-smooth muscle actin and vimentin. Consumption of HFD induced dysregulation of AMP-activated protein kinase/glycogen synthase kinase-3 beta signaling in cardiac tissue of rats. This was coupled with down-regulation of nuclear factor erythroid-2-related factor 2 (Nrf2) and its downstream targets in cardiac tissue of HFD-fed rats, as well as enhanced the oxidative stress and inflammatory burden. These results demonstrate that moderate-term consumption of HFD can enhance oxidative stress, induce inflammation, and activate the fibrogenic pathways in cardiac tissue of rats which stimulate fibrotic remodeling. Our findings may implicate the dysregulation of Nrf2 signaling as a putative mechanism for this effect.

中文翻译：

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高脂饮食喂养大鼠心脏中核因子红系2相关因子2信号的失调和纤维生成途径的激活。

高脂饮食（HFD）引起的肥胖对心脏预后产生不利影响；然而，HFD摄入量对心肌重塑的影响及其潜在机制仍然难以捉摸。这项研究旨在检查HFD喂养的大鼠心脏组织的组织学和分子变化。给八周大的雄性Wistar大鼠喂食HFD或正常食物饮食16周，然后评估其代谢和心脏稳态的变化（每组n = 10）。HFD治疗16周可导致肥胖，血脂异常和葡萄糖耐量改变，但无高血压。对Masson的三色染色心脏切片进行组织学检查，发现其纤维化变化很大，而免疫印迹分析显示，喂食HFD的大鼠心脏组织中I，III型胶原和纤连蛋白的表达较高。在喂食HFD的大鼠的心脏组织中，转化生长因子β1的表达及其下游靶标Smad3的磷酸化显着增加。喂食HFD的大鼠心脏促进了内皮-间充质转化的激活，这由血小板内皮细胞粘附分子-1的下调，而α-平滑肌肌动蛋白和波形蛋白的上调来证明。HFD诱导大鼠心脏组织中AMP激活的蛋白激酶/糖原合酶激酶3β信号转导的失调。这与HFD喂养大鼠心脏组织中核因子红系-2相关因子2（Nrf2）及其下游靶点的下调相结合，并增强了氧化应激和炎症负担。这些结果表明，适量食用HFD可以增强氧化应激，诱导炎症，并激活大鼠心脏组织中的纤维化途径，从而刺激纤维化重构。我们的发现可能暗示Nrf2信号的失调是这种作用的推测机制。