Scientific Reports ( IF 3.8 ) Pub Date : 2023-10-06 , DOI: 10.1038/s41598-023-44030-9
Stephanie D Burr 1, 2 , Yongbin Chen 1 , Christopher P Hartley 3 , Xianda Zhao 3 , Jun Liu 1, 2
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Dietary saturate fatty acids (SFAs) have been consistently linked to atherosclerosis and obesity, both of which are characterized by chronic inflammation and impaired lipid metabolism. In comparison, the effects of linoleic acid (LA), the predominant polyunsaturated fatty acid in the Western diet, seem to diverge. Data from human studies suggest a positive association between high dietary intake of LA and the improvement of cardiovascular risk. However, excessive LA intake has been implicated in the development of obesity. Concerns have also been raised on the potential pro-inflammatory properties of LA metabolites. Herein, by utilizing a mouse model with liver-specific Ldlr knockdown, we directly determined the effects of replacing SFAs with LA in a Western diet on the development of obesity and atherosclerosis. Specifically, mice treated with a Ldlr ASO were placed on a Western diet containing either SFA-rich butter (WD-B) or LA-rich corn oil (WD-CO) for 12 weeks. Despite of showing no changes in body weight gain or adiposity, mice on WD-CO exhibited significantly less atherosclerotic lesions compared to those on WD-B diet. Reduced lesion formation in the WD-CO-fed mice corresponded with a reduction of plasma triglyceride and cholesterol content, especially in VLDL and LDL, and ApoB protein levels. Although it increased expression of proinflammatory cytokines TNF-α and IL-6 in the liver, WD-CO did not appear to affect hepatic injury or damage when compared to WD-B. Collectively, our results indicate that replacing SFAs with LA in a Western diet could reduce the development of atherosclerosis independently of obesity.
中文翻译:
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在西方饮食中用亚油酸替代饱和脂肪酸可减轻小鼠模型中的动脉粥样硬化,并可诱导消除肝脏 LDL 受体
膳食饱和脂肪酸(SFA)一直与动脉粥样硬化和肥胖有关,这两者的特点都是慢性炎症和脂质代谢受损。相比之下,亚油酸(LA)(西方饮食中主要的多不饱和脂肪酸)的作用似乎有所不同。人体研究数据表明,高膳食 LA 摄入量与心血管风险改善之间呈正相关。然而,过量的 LA 摄入与肥胖的发生有关。人们还对 LA 代谢物潜在的促炎特性表示担忧。在此,通过利用肝脏特异性 Ldlr 敲低的小鼠模型,我们直接确定了西方饮食中用 LA 替代 SFA 对肥胖和动脉粥样硬化发展的影响。具体来说,用 Ldlr ASO 治疗的小鼠被置于含有富含 SFA 的黄油 (WD-B) 或富含 LA 的玉米油 (WD-CO) 的西方饮食中 12 周。尽管体重增加或肥胖没有变化,但与 WD-B 饮食的小鼠相比,WD-CO 饮食的小鼠表现出明显较少的动脉粥样硬化病变。喂食 WD-CO 的小鼠中病变形成的减少与血浆甘油三酯和胆固醇含量的降低相对应,尤其是 VLDL 和 LDL 以及 ApoB 蛋白水平的降低。尽管 WD-CO 增加了肝脏中促炎细胞因子 TNF-α 和 IL-6 的表达,但与 WD-B 相比,WD-CO 似乎并未影响肝损伤或损害。总的来说,我们的结果表明,在西方饮食中用 LA 替代 SFA 可以减少动脉粥样硬化的发展,而与肥胖无关。