Hypolipidemic effect of β, β′-tetramethyl hexadecanedioic acid (MEDICA 16) in hyperlipidemic JCR: LA-corpulent rats

James C. Russell*, Peter J. Dolphin, Morad Hameed, Bruce Stewart, Dorothy G. Koeslag, Gene Rose-Kahn, Jacob Bar-Tana

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Short-term treatment of male and female obese JCR:LA-corpulent rats with β,β′-tetramethyl hexadecanedioic acid (MEDICA 16) resulted in a marked decrease (as much as 80%) in plasma triglyceride values, with a concomitant decrease in the highly elevated very low density lipoprotein (VLDL) levels of the corpulent rat. There were modest decreases in cholesterol levels and increases in low density lipoprotein and high density lipoprotein lipids. The concentrations of apolipoproteins C-II and C-III were decreased in both the whole-serum and the VLDL fractions. Food consumption, rate of weight gain, fasting insulin levels, and the integrated insulin response to an intravenous glucose load remained unaffected. The decrease in plasma VLDL may be accounted for by inhibition of liver long-chain fatty acid synthesis at the level of ATP citrate lyase, with a concomitant reduction of VLDL triglyceride production by the liver. This decrease in plasma VLDL production was accompanied by a twofold to threefold increase in the triglyceride and cholesterol components of the low density lipoprotein and high density lipoprotein fractions, together with a twofold to fourfold decrease in plasma apolipoprotein, indicating that activation of plasma VLDL catabolism may further account for the overall hypolipidemic effect induced by MEDICA 16. The overall hypolipidemic effect of MEDICA 16 may be expected to inhibit the spontaneous atherogenic sequelae induced in the corpulent rat by severe VLDL hyperlipidemia.

Original languageEnglish
Pages (from-to)602-609
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume11
Issue number3
StatePublished - 1991

Keywords

  • Hypertriglyceridemia
  • JCR
  • LA corpulent rat
  • MEDICA 16
  • Obesity
  • Very low density lipoproteins

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