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Journal of Lipid Research, Vol 29, 431-441, Copyright © 1988 by Lipid Research, Inc.

ARTICLES

Hypolipidemic effect of beta, beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) in normal and nephrotic rats

J Bar-Tana, G Rose-Kahn, B Frenkel, Z Shafer and M Fainaru
Department of Biochemistry, Jerusalem, Israel.

Treatment of normal or puromycin aminonucleoside-nephrotic rats, kept on a balanced Purina chow diet, with beta, beta'-tetramethyl- substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana, J., G. Rose- Kahn, and M. Srebnik. 1985. J. Biol. Chem. 260: 8404-8410) resulted in an acute reversible inhibition of liver lipogenesis and cholesterogenesis with a concomitant hypolipidemic effect which was sustained as long as the drug was administered. The hypolipidemic effect in normal and nephrotic rats consisted of 70-80% and 40-60% reduction in plasma VLDL-triacylglycerols and cholesterol, respectively, with a respective increase in the HDL-cholesterol/(VLDL + LDL)-cholesterol ratio. The observed hypolipidemic effect was accompanied by a 10-fold decrease in VLDL-apoC-III content with a concomitant enrichment of the VLDL fraction by VLDL remnants having an increased apoB-100/apoB-48 ratio. The pharmacological reduction of VLDL by MEDICA 16 may offer a treatment mode of choice for selected hyperlipidemic states.
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