Abstract 3200: Free Fatty Acid Infusion and Vascular Function in Obese African-Americans with the Metabolic Syndrome
Background: Increased levels of free fatty acids (FFA) are thought to contribute to the pathogenesis of hypertension (HTN); however, the mechanisms are poorly understood. Accordingly, we evaluated the effects of increased FFA on blood pressure (BP), insulin resistance, the renin angiotensin-aldosterone system (RAAS), and endothelial function. Moreover, we determined the effects of rosiglitazone (an insulin sensitizing agent) in obese African Americans (AA) with the metabolic syndrome.
Methods: Nineteen obese AA normoten-sive diabetics (41±2 yr, body-mass index 38±1 kg/m2) and 13 obese AA normotensive nondiabetic subjects (42±1 yr, body-mass index 36±2 kg/m2) received sequential 48-h infusion of Intralipid (20%, 40 ml/h) plus heparin (250 units/h) vs. normal saline (40 ml/h) plus heparin. The subjects were then treated with rosiglitazone (4 mg/day) for 4 weeks, and a similar infusion was performed. We measured changes in blood pressure and levels of glucose, insulin, renin, aldosterone, and C-peptide during infusions. Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD) and by changes in vascular biomarkers.
Results: Intralipid infusion after 48 h resulted in a rise of 12±2 mm Hg in systolic BP and 8±2 mm Hg in diastolic BP from baseline (p<0.05 vs. saline). The rise in FFA levels (from 0.5±0.1 to 1.7±0.2 mmol/L) resulted in increased insulin resistance and in a 14% reduction in FMD. There were no differences in renin and aldosterone levels. The levels of C-reactive protein (CRP) increased by 2-fold at 48 h of lipid infusion (baseline: 0.48±0.10; 48 h: 0.90±0.12 mg/L, p<0.005). Levels of soluble interleukin-6 (IL-6) increased significantly as well (base-line:15.1±1.6; 48 h: 40.4±5.7 ng/dl, p<0.005). Rosiglitazone therapy blunted the FFA-induced rise in BP and reversed the FFA-induced reduction in FMD. Furthermore, rosiglitazone therapy suppressed the FFA-induced rise in CRP and IL-6 in all subjects.
Conclusions: In addition to the well-known effect on insulin resistance, increased FFA results in the development of HTN as the result of an acute inflammatory response and endothelial dysfunction. Rosiglitazone prevents FFA-induced vascular toxicity in obese AA subjects with the metabolic syndrome.