Departments of Pediatrics (CLK), Medicine (CLK and KC), and Medical Biostatistics (JYB), University of Vermont, Burlington, VT, and the Stedman Nutrition and Metabolism Center (RS, JB, OI, TRK, and DMM) and Departments of Medicine (TRK and DMM) and Pharmacology and Cancer Biology (DMM), Duke University, Durham, NC.
Am J Clin Nutr. 2014 Mar;99(3):436-45. doi: 10.3945/ajcn.113.070557. Epub 2014 Jan 15.
Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid (PA) to oleic acid (OA) increase risk of cardiovascular disease (CVD).
To gain additional insights into the relative effect of dietary fatty acids and their metabolism on CVD risk, we sought to identify a metabolomic signature that tracks with diet-induced changes in blood lipid concentrations and whole-body fat oxidation.
We applied comprehensive metabolomic profiling tools to biological specimens collected from 18 healthy adults enrolled in a crossover trial that compared a 3-wk high-palmitic acid (HPA) with a low-palmitic acid and high-oleic acid (HOA) diet.
A principal components analysis of the data set including 329 variables measured in 15 subjects in the fasted state identified one factor, the principal components analysis factor in the fasted state (PCF1-Fasted), which was heavily weighted by the PA:OA ratio of serum and muscle lipids, that was affected by diet (P < 0.0001; HPA greater than HOA). One other factor, the additional principal components analysis factor in the fasted state (PCF2-Fasted), reflected a wide range of acylcarnitines and was affected by diet in women only (P = 0.0198; HPA greater than HOA). HOA lowered the ratio of serum low-density lipoprotein to high-density lipoprotein (LDL:HDL) in men and women, and adjustment for the PCF1-Fasted abolished the effect. In women only, adjustment for the PCF2-Fasted eliminated the HOA-diet effect on serum total- and LDL-cholesterol concentrations. The respiratory exchange ratio in the fasted state was lower with the HPA diet (P = 0.04), and the diet effect was eliminated after adjustment for the PCF1-Fasted. The messenger RNA expression of the cholesterol regulatory gene insulin-induced gene-1 was higher with the HOA diet (P = 0.008).
These results suggest that replacing dietary PA with OA reduces the blood LDL concentration and whole-body fat oxidation by modifying the saturation index of circulating and tissue lipids. In women, these effects are also associated with a higher production and accumulation of acylcarnitines, possibly reflecting a shift in fat catabolism.
流行病学证据表明，棕榈酸（PA）与油酸（OA）比值较高的饮食会增加心血管疾病（CVD）的风险。
为了更深入地了解饮食脂肪酸及其代谢对 CVD 风险的相对影响，我们试图确定一种代谢组学特征，该特征可跟踪与饮食诱导的血液脂质浓度和全身脂肪氧化变化相关的变化。
我们应用综合代谢组学分析工具，对 18 名参加交叉试验的健康成年人的生物样本进行了分析，该试验比较了高棕榈酸（HPA）与低棕榈酸和高油酸（HOA）饮食 3 周。
对包括 15 名空腹受试者在内的 329 个变量的数据集进行主成分分析，确定了一个主要成分分析因子（空腹状态下的主要成分分析因子，即 PCF1-Fasted），该因子主要由血清和肌肉脂质中的 PA:OA 比值加权，受饮食影响（P<0.0001；HPA 大于 HOA）。另一个主要成分分析因子（空腹状态下的附加主要成分分析因子，即 PCF2-Fasted），反映了广泛的酰基肉碱，并仅在女性中受饮食影响（P=0.0198；HPA 大于 HOA）。HOA 降低了男性和女性血清低密度脂蛋白与高密度脂蛋白（LDL:HDL）的比值，调整 PCF1-Fasted 后消除了该作用。仅在女性中，调整 PCF2-Fasted 后消除了 HOA 饮食对血清总胆固醇和 LDL 胆固醇浓度的影响。HPA 饮食时空腹状态下的呼吸交换率较低（P=0.04），调整 PCF1-Fasted 后消除了饮食的影响。HOA 饮食时胆固醇调节基因胰岛素诱导基因-1 的信使 RNA 表达较高（P=0.008）。
这些结果表明，用 OA 替代饮食中的 PA 可通过改变循环和组织脂质的饱和度指数来降低血液 LDL 浓度和全身脂肪氧化。在女性中，这些作用还与酰基肉碱的产生和积累增加有关，这可能反映了脂肪分解代谢的变化。
