Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA.
Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic in Rochester, Guggenheim Building 14-11A, 222 3Rd Avenue SW, Rochester, MN, 55905, USA.
Sci Rep. 2023 Oct 6;13(1):16832. doi: 10.1038/s41598-023-44030-9.
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.
膳食饱和脂肪酸（SFAs）一直与动脉粥样硬化和肥胖有关，这两者都以慢性炎症和脂质代谢受损为特征。相比之下，亚油酸（LA）的作用似乎有所不同，LA 是西方饮食中主要的多不饱和脂肪酸。来自人类研究的数据表明，LA 高摄入量与心血管风险改善之间存在正相关。然而，过量的 LA 摄入与肥胖的发展有关。人们还对 LA 代谢物的潜在促炎特性表示担忧。在此，我们利用肝脏特异性 Ldlr 敲低的小鼠模型，直接确定用 LA 替代西方饮食中的 SFAs 对肥胖和动脉粥样硬化发展的影响。具体来说，用 Ldlr ASO 处理的小鼠被置于富含 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 WD-CO 组的体重增加或肥胖程度没有变化，但与 WD-B 饮食组相比，WD-CO 饮食组的动脉粥样硬化病变明显减少。WD-CO 喂养的小鼠的病变形成减少与血浆甘油三酯和胆固醇含量的减少相对应，尤其是 VLDL 和 LDL 以及 ApoB 蛋白水平。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，它似乎不会影响肝脏损伤或损害。总之，我们的结果表明，用 LA 替代西方饮食中的 SFAs 可以独立于肥胖来减少动脉粥样硬化的发展。
