Abstract：
Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids β-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.
摘要：
随着世界范围内肥胖患病率的增加,越来越多的流行病学研究逐渐认识到高热量饮食的有害影响。然而,隐蔽性和慢性因果关系粉饰了它的不健康特征。鉴于一个巧妙的机制协调代谢适应高脂肪高果糖（HFF）饮食和纵容其脂毒性，在这项研究中，诱导了一个实验性的肥胖大鼠/小鼠模型，并进行了比较转录组学分析来探索这个谜。我们的结果表明，HFF饮食消耗改变了转录组模式，并且不同的高热量饮食喂养的大鼠/小鼠表现出不同的肝脏转录组。RT-qPCR和Western印迹验证证实SREBP1-FASN参与从头脂肪生成部分介导的代谢自适应。此外，肝脏ACSL1-CPT1A-CPT2通路参与脂肪酸β-氧化，在对HFF的代谢适应中起关键作用。总的来说，我们的发现丰富了慢性适应机制的知识，也为未来的研究提供了启示。同时,我们的研究结果还表明,恢复脂肪酸代谢命运的努力可能是对抗HFF饮食所挑战的肥胖和相关脂肪变性和胰岛素抵抗的有希望的途径.
