Journal of Lipid Research, Vol 30, 1711-1718, Copyright © 1989 by Lipid Research, Inc.

ARTICLES

Alkylthioacetic acids (3-thia fatty acids) as non-beta-oxidizable fatty acid analogues: a new group of hypolipidemic drugs. III. Dissociation of cholesterol- and triglyceride-lowering effects and the induction of peroxisomal beta-oxidation

A Aarsland, N Aarsaether, J Bremer and RK Berge
Laboratory of Clinical Biochemistry, University of Bergen, Norway.

Previous work in this laboratory indicated that sulfur-substituted fatty acid analogues, 1.10-bis(carboxymethylthio)decane and alkylthioacetic acid, both non-beta-oxidizable compounds, and the beta- oxidizable alkylthiopropionic acid (1) caused, to different extents, dose-related hepatomegaly and proliferation of peroxisomes and enhanced peroxisomal fatty acid beta-oxidation. In the present study, treatment of normolipidemic rats with alkylthioacetic acid resulted in a dose- and time-dependent decrease in serum cholesterol and serum and liver triglycerides to an extent comparable to that of the 3-thiadicarboxylic acid. At hypolipidemic doses, alkylthioacetic acid caused no hepatomegaly, did not significantly alter peroxisome morphology, and only marginally affected peroxisomal beta-oxidation activity. Only at the highest, nonpharmacological doses of alkylthioacetic acid were these hepatic parameters increased, although to a lesser extent than by the 3-thiadicarboxylic acid. Hence, on the basis of dose- and time- related studies of the two compounds, data indicate that the hypotriglyceridemia and hypocholesterolemia were dissociated from induction of peroxisomal beta-oxidation and peroxisome proliferation. Palmitic acid and hexadecanedioic acid, both beta-oxidizable fatty acids, only marginally affected the serum and liver parameters. The beta-oxidizable fatty acid analogue, alkylthiopropionic acid lowered the serum triglycerides in normolipidemic rats. In contrast to the 3- thiadicarboxylic acid and alkylthioacetic acid, alkylthiopropionic acid treatment at hypolipidemic doses caused accumulation of triglycerides in the liver.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. M. Bivol, R. K. Berge, and B. M. Iversen Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R438 - R447. [Abstract] [Full Text] [PDF]

				L. M. Bivol, R. K. Berge, and B. M. Iversen Differential effect of tetradecythioacetic acid on the renin-angiotensin system and blood pressure in SHR and 2-kidney, 1-clip hypertension Am J Physiol Renal Physiol, September 1, 2007; 293(3): F839 - F845. [Abstract] [Full Text] [PDF]

				Z. A. Muna, K. Doudin, J. Songstad, R. J. Ulvik, and R. K. Berge Tetradecylthioacetic Acid Inhibits the Oxidative Modification of Low Density Lipoprotein and 8-Hydroxydeoxyguanosine Formation In Vitro Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3255 - 3262. [Abstract] [Full Text]