Statins affect the production of long chain polyunsaturated fatty acids (PUFA), both in vitro and in vivo. Various studies have shown the effects of statins on the pattern of n-6 fatty acids (FA), but limited attention has been paid to the n-3 FA. We investigated, in THP-1 and in HepG2 cells, the effects of simvastatin on the conversion of the 18C FA precursors in the n-3 and n-6 series, [1-14C] (alpha)-linolenic acid ((alpha)-LNA) and [1- 14C] linoleic acid (LA) respectively, and on the metabolism of [1-14C] stearic acid (SA). THP-1 cells, as in the case of LA, actively converted (alpha)-LNA to its products, and after simvastatin treatment, the total conversion was significantly increased (from 57.2 (plus or minus) 7.2 to 74.3 (plus or minus) 8.5%, p < 0.05). HepG2 cells also converted LA and (alpha)-LNA, but simvastatin increased significantly only the conversion of LA (9.5 (plus or minus) 1.9% versus 23.8 (plus or minus) 5.1%, p < 0.02). SA conversion was similar in untreated cells (about 50%), while statin increased the production of oleic acid in HepG2, but in THP-1 cells there was a decrease. In conclusion, LA, (alpha)-LNA and SA are differentially metabolized in THP-1 and in HepG2 cells and their increased conversion by simvastatin is lower in HepG2 than in THP-1. These differences may reflect the distinct features of the two cell lines: monocytes, precursors of phagocytic cells, versus hepatocytes with mainly metabolic functions. Substantial differences concern also cellular FA pools: structural in THP-1 cells, and also depot, resulting in sequestering of the substrates, in HepG2. The greater n-3 FA metabolism in THP-1 cells may have favourable functional effects. (copyright) 2005 Elsevier Inc. All rights reserved.
|Titolo:||Differential modulation by simvastatin of the metabolic pathways in the n-9, n-6 and n-3 fatty acid series, in human monocytic and hepatocytic cell lines|
|Parole Chiave:||α-Linolenic acid; Cultured cells; Fatty acid metabolism; Linoleic acid; Simvastatin; Stearic acid|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bcp.2005.01.006|
|Appare nelle tipologie:||01 - Articolo su periodico|