HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rise, P. Articles by Galli, C. Search for Related Content PubMed PubMed Citation Articles by Rise, P. Articles by Galli, C. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 38, 1299-1307, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Effects of simvastatin on the metabolism of polyunsaturated fatty acids and on glycerolipid, cholesterol, and de novo lipid synthesis in THP-1 cells

P Rise, C Colombo and C Galli
Institute of Pharmacological Sciences, University of Milan, Milano, Italy.

In the monocytic THP-1 cells, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor simvastatin (5 microM) enhances the conversion of exogenous linoleic (18:2 n-6) and eicosapentaenoic (20:5 n-3) acids to their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives, and this effect is associated with changes in the desaturation steps. In addition, formation of monounsaturated fatty acids from endogenously synthesized precursors is increased. These metabolic changes lead to elevated LC-PUFA and fatty acid (FA) unsaturation in cells. The effects of simvastatin on FA metabolism are associated with increased synthesis of triglycerides from glycerol. The dose-effect relationships for the activity of simvastatin on total linoleic acid (LA) conversion and cholesterol synthesis reveal that enhancement of PUFA metabolism is already maximal at 0.5 microM simvastatin, whereas cholesterol synthesis is further inhibited by concentrations of simvastatin up to 5 microM. The effects of 5 microM simvastatin on PUFA metabolism are partially prevented by mevalonate (1 mM) and geranylgeraniol (5 microM) but not by farnesol (10 microM). These data indicate that HMG-CoA inhibitors have profound effects on PUFA metabolism, and that the pathways for cholesterol and PUFA synthesis are mutually modulated.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Jula, J. Marniemi, T. Ronnemaa, A. Virtanen, and R. Huupponen Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men: A Randomized Controlled Trial Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1952 - 1959. [Abstract] [Full Text] [PDF]

				C. Banfi, L. Mussoni, P. Rise, M. G. Cattaneo, L. Vicentini, F. Battaini, C. Galli, and E. Tremoli Very Low Density Lipoprotein–Mediated Signal Transduction and Plasminogen Activator Inhibitor Type 1 in Cultured HepG2 Cells Circ. Res., July 23, 1999; 85(2): 208 - 217. [Abstract] [Full Text] [PDF]