Effects of Acipimox on the metabolism of free fatty acids and very low lipoprotein triglyceride

The mechanism of triglyceride lowering by Acipimox, a nicotine acid analogue, was examined in a group of five moderately hypertriglyceridemic male rhesus monkeys. Two experiments were designed to examine the effect of the drug on lipid and glucose metabolism in nondiabetic, insulin-resistant animals...

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Bibliographic Details
Published in:Acta diabetologica 1995-12, Vol.32 (4), p.279-283
Main Authors: Hannah, J S, Bodkin, N L, Paidi, M S, Anh-Le, N, Howard, B V, Hansen, B C
Format: Article
Language:English
Subjects:
Animals
Blood Glucose - drug effects
Blood Glucose - metabolism
Cholesterol, LDL - blood
Cholesterol, VLDL - blood
Eating
Fatty Acids, Nonesterified - blood
Glucose Clamp Technique
Glycerol - metabolism
Humans
Hypolipidemic Agents - pharmacology
Infusions, Intravenous
Insulin - administration & dosage
Insulin - pharmacology
Lipoproteins, VLDL - blood
Macaca mulatta
Male
Pyrazines - pharmacology
Reference Values
Triglycerides - blood
Tritium
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Summary:The mechanism of triglyceride lowering by Acipimox, a nicotine acid analogue, was examined in a group of five moderately hypertriglyceridemic male rhesus monkeys. Two experiments were designed to examine the effect of the drug on lipid and glucose metabolism in nondiabetic, insulin-resistant animals. A single dose of Acipimox (8 mg/kg) given with a meal lowered the plasma free fatty acids (FFA) significantly at 4 h (0.102 +/- 0.008 vs 0.154 +/- 0.020 g/l; mean +/- SEM; P < 0.03); however, FFA concentrations returned to control levels at 6 h. Chronic administration of Acipimox (16 mg/kg q. i. d.) for 2 months produced a 31% reduction in triglyceride concentration (P < 0.05) and a significant decrease in low density lipoprotein (LDL)-cholesterol (P < 0.04), without changes in insulin action as measured by the hyperinsulinemic euglycemic clamp. Fasting FFA concentrations were not significantly altered by chronic treatment (0.163 +/- 0.013 versus 0.140 +/- 0.034 g/l). Fatty acid metabolic studies indicated increases in FFA transport (203.7 +/- 59.1 versus 136.1 +/- 26.6 microEq/min; P < 0.05), while FFA fractional clearance rate (FCR) was unchanged. Very low density lipoprotein triglyceride (VLDL-Tg) metabolic experiments, using [3H]glycerol, showed increases in production and FCR with the drug. Increased VLDL-Tg clearance, in spite of increased production of VLDL, appears to be the mechanism by which triglycerides are lowered upon chronic Acipimox administration.
ISSN:0940-5429