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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.

Risé P, Ghezzi S, Priori I, Galli C

Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy. patrizia.rise@unimi.it

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-(14)C] alpha-linolenic acid (alpha-LNA) and [1-(14)C] linoleic acid (LA) respectively, and on the metabolism of [1-(14)C] 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+/-7.2 to 74.3+/-8.5%, p<0.05). HepG2 cells also converted LA and alpha-LNA, but simvastatin increased significantly only the conversion of LA (9.5+/-1.9% versus 23.8+/-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.

Published 14 March 2005 in Biochem Pharmacol, 69(7): 1095-100.
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