Palmitic acid in HDL is associated to low apo A-I fractional catabolic rates in vivo.

BACKGROUND: HDL becomes enriched with non-esterified fatty acids (NEFAs) in some pathologies, such as nephrotic syndrome, as well as after aerobic exercise. However, little is known about the impact of NEFAs on HDL metabolism. We investigated the effects of one NEFA, the palmitic acid, on HDL structure and catabolism. METHODS: HDL enrichment with palmitic acid (HDLPal) was performed by fusing phosphatidyl choline small unilamellar vesicles containing the NEFA with human HDL isolated from a pool of 5 normolipidemic plasma. HDL enriched only with phosphatidyl choline (HDLPhl) and native HDL (HDLCtrl) were included as controls. RESULTS: As expected, HDLPal surface charge density was higher than HDLPhl and HDLCtrl (2014.4+/-164.8 vs. 1682.7+/-149.5 and 1758.2+/-124.3-esu/cm2, respectively, p<0.05). Both, HDLPal and HDLPhl were better substrates for cholesteryl esters transfer protein (CETP) than HDLCtrl (% of transfer, 13.02+/-3.8 and 12.7+/-4.5 vs. 7.8+/-2.7% in 16 h, respectively, p<0.05). HDLPal apo A-I catabolism in vivo, as performed in New Zealand white rabbits by exogenous radiolabeling, was markedly lower than that of HDLPhl and HDLCtrl (fractional catabolic rate, 0.019+/-0.008 vs. 0.030+/-0.005 and 0.047+/-0.003 h-1, respectively, p<0.001), suggesting that negative charge is inversely related to HDL-apo A-I catabolism. CONCLUSIONS: Enrichment with palmitic acid increases the negative electric charge of HDL at physiological pH, contributes to decrease their catabolism, and is associated to an enhanced lipid transfer by CETP that has been related to the atherogenic process.