Increasing Plasma Free Fatty Acids in Healthy Subjects Induces Aortic Distensibility Changes Seen in Obesity

Background— 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. Methods and Results— 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). Conclusions— 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.