University of Oxford Centre for Clinical Magnetic Resonance Research and the Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Circ Cardiovasc Imaging. 2012 May 1;5(3):367-75. doi: 10.1161/CIRCIMAGING.111.971804. Epub 2012 Apr 5.
Elevated free fatty acid (FFA) levels are known to impair aortic elastic function. In obesity, FFA levels are elevated and aortic distensibility (AD) reduced in a pattern that predominantly affects the distal aorta. Despite this, the role of FFAs in obesity-related aortic stiffness remains unclear.
Using vascular MRI, we aimed to determine if (1) FFA level correlated with AD in obesity; and (2) whether elevating FFA acutely and subacutely in normal-weight subjects reproduced the distal pattern of AD change in obesity. To do this, regional AD was recorded in 35 normal-weight and 70 obese subjects and then correlated with FFA levels. When compared with normal weight, obesity was associated with reduced AD in a pattern predominantly affecting the distal aorta (ascending aorta by -22%, proximal descending aorta by -25%, and abdominal aorta by -35%; P<0.001). After controlling for age, blood pressure, and body mass index, FFA levels remained negatively correlated with abdominal AD (r=-0.43, P<0.01). In 2 further normal-weight groups, AD was recorded before and after elevation of FFA levels with intralipid infusion (by +535%, n=9) and a 5-day high-fat, low-carbohydrate diet (by +48%, n=14).
Both intralipid infusion and a low-carbohydrate diet resulted in reduced abdominal AD (infusion -22%, diet -28%; both P<0.05), reproducing the distal pattern AD reduction seen in obesity. These findings suggest that elevated FFA impair AD in obesity and provide a potential therapeutic target to improve aortic elastic function in obesity.
已知游离脂肪酸（FFA）水平升高会损害主动脉弹性功能。在肥胖中，FFA 水平升高，主动脉顺应性（AD）降低，主要影响远端主动脉。尽管如此，FFA 在肥胖相关的主动脉僵硬中的作用仍不清楚。
使用血管 MRI，我们旨在确定（1）FFA 水平与肥胖中的 AD 是否相关；（2）在正常体重受试者中急性和亚急性升高 FFA 是否会再现肥胖中 AD 改变的远端模式。为此，在 35 名正常体重和 70 名肥胖受试者中记录了局部 AD，然后将其与 FFA 水平相关联。与正常体重相比，肥胖与 AD 的降低模式相关，主要影响远端主动脉（升主动脉降低 22%，近端降主动脉降低 25%，腹主动脉降低 35%；P<0.001）。在校正年龄、血压和体重指数后，FFA 水平仍与腹主动脉 AD 呈负相关（r=-0.43，P<0.01）。在另外两个正常体重组中，通过脂肪乳剂输注（增加 535%，n=9）和 5 天低碳水化合物高脂肪饮食（增加 48%，n=14），在 FFA 水平升高前后记录了 AD。
脂肪乳剂输注和低碳水化合物饮食均导致腹主动脉 AD 降低（输注降低 22%，饮食降低 28%；均 P<0.05），再现了肥胖中观察到的 AD 降低的远端模式。这些发现表明，升高的 FFA 会损害肥胖中的 AD，并为改善肥胖中的主动脉弹性功能提供了一个潜在的治疗靶点。
