title: Increasing plasma free fatty acids in healthy subjects induces aortic distensibility changes seen in obesity.
abstract: 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.
  
  
  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.
authors.affiliation: University of Oxford Centre for Clinical Magnetic Resonance Research and the Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. oliver.rider@gmail.com
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rider
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Holloway
authors.forename: Yaso
authors.initials: Y
authors.lastname: Emmanuel
authors.forename: Edward
authors.initials: E
authors.lastname: Bloch
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D000328:Adult; D001011:Aorta / Q000503:physiopathology*; D015992:Body Mass Index; D015331:Cohort Studies; D003187:Compliance; D050528:Diet, Carbohydrate-Restricted / Q000379:methods; D059305:Diet, High-Fat / Q000379:methods; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood* / Q000503:physiopathology*; D059289:Vascular Stiffness
chemical_list: D005230:Fatty Acids, Nonesterified