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

Abstract

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.