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.
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.
Risé
Patrizia
P
Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy. patrizia.rise@unimi.it
Ghezzi
Silvia
S
Priori
Ilaria
I
Galli
Claudio
C
D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D045744:Cell Line, Tumor; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms; D008745:Methylation; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D013229:Stearic Acids / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D013229:Stearic Acids; C031183:stearic acid; D019821:Simvastatin