Lipids

, Volume 12, Issue 1, pp 1–9 | Cite as

Hypolipidemic activity of (−)-hydroxycitrate

  • Ann C. Sullivan
  • Joseph Triscari
  • James G. Hamilton
  • Joseph A. Ontko
Symposium: Hyperlipidemia Presented at the AOCS 67 th Annual Spring Meeting New Orleans, Louisiana

Abstract

The influence of (−)-hydroxycitrate, a potent competitive inhibitor of adenosine triphosphate (ATP) citrate lyase, on serum triglyceride and cholesterol levels, and in vitro and in vivo rates of hepatic fatty acid and cholesterol synthesis was investigated in normal and hyperlipidemic rat model systems. (−)-Hydroxycitrate reduced equivalently the biosynthesis of triglycerides, phospholipids, cholesterol, diglycerides, cholesteryl esters, and free fatty acids in isolated liver cells. In vivo hepatic rates of fatty acid and cholesterol synthesis determined in meal-fed normolipidemic rats were suppressed significantly by the oral administration of (−)-hydroxycitrate for 6 hr, when control animals exhibited maximal rates of lipid synthesis; serum triglyceride and cholesterol levels were significantly reduced by (−)-hydroxycitrate. In two hypertryglyceridemic models—the genetically obese Zucker rat and the fructose-treated rat—elevated triglyceride levels were due, in part, to enhanced hepatic rates of fatty acid synthesis. (−)-Hydroxycitrate significantly reduced the hypertriglyceridemia and hyperlipogenesis in both models. The marked hypertriglyceridemia exhibited by the triton-treated rat was only minimally due to increased hepatic lipogenesis; (−)-hydroxycitrate significantly inhibited both serum triglyceride levels and lipogenesis in this model.

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Copyright information

© American Oil Chemists’ Society 1977

Authors and Affiliations

  • Ann C. Sullivan
    • 1
    • 2
  • Joseph Triscari
    • 1
    • 2
  • James G. Hamilton
    • 1
    • 2
  • Joseph A. Ontko
    • 2
  1. 1.Department of Biochemical Nutrition, Roche Research CenterHoffmann-La Roche Inc.Nutley
  2. 2.Cardiovascular Research ProgramOklahoma Medical Research FoundationOklahoma City

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