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

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Abstract

The mechanism of triglyceride lowering by Acipimox, a nicotinic 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;\(\bar x\)±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 μEq/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.

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Authors and Affiliations

  1. Medlantic Research Institute, G. Hyman Research Building, 108 Irving Street, NW, 20010, Washington, DC, USA

    J. S. Hannah, M. S. Paidi, N. Anh-Le & B. V. Howard

  2. Diabetes and Obesity Research Center, University of Maryland at Baltimore, 10 S. Pine Street, 21201, Baltimore, MD, USA

    N. L. Bodkin & B. C. Hansen

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  1. J. S. Hannah
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  2. N. L. Bodkin
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  3. M. S. Paidi
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  4. N. Anh-Le
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  5. B. V. Howard
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  6. B. C. Hansen
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Hannah, J.S., Bodkin, N.L., Paidi, M.S. et al. Effects of Acipimox on the metabolism of free fatty acids and very low density lipoprotein triglyceride. Acta Diabetol 32, 279–283 (1995). https://doi.org/10.1007/BF00576264

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  • DOI: https://doi.org/10.1007/BF00576264

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