Effect of nicotinic acid administration on hepatic very low density lipoprotein-triglyceride production

Our objective was to examine very low density lipoprotein-triglyceride (VLD L-TG) kinetics after chronic and acute administration of nicotinic acid (NA ). Incorporation of [1,2,3,4-(13) C-4]palmitate and [2-C-13(1)]glycerol int o VLDL-TG was measured in five healthy, normolipidemic women. Each subject was studied twice; the 4-day hospital stays were separated by 1 mo, during which time doses of NA were increased to 2 g/day (500 mg, 4 times/day). Dur ing posttreatment study, 500 mg of NA were administered acutely at 0800. Un der baseline postabsorptive conditions, incorporation curves from C-13-labe led free fatty acid (FFA) and C-13-labeled glycerol were superimposable, an d VLDL-TG kinetics were in agreement (t(1/2) = 1.4 +/- 0.3 and 1.3 +/- 0.3 h, and production rates = 27.2 +/- 6.1 and 28.5 +/- 5.3 g/day, respectively ). In the postabsorptive state after chronic NA therapy, VLDL-TG concentrat ions and production rates were lower despite a trend toward elevated plasma FFA concentrations and fluxes. After the acute dose of NA, plasma FFA conc entrations and flux fell dramatically, and there was a virtual halt to VLDL -TG production, which continued throughout the 6-h period after NA, despite a marked rebound overshoot in serum FFA concentrations and flux after hour 2. Plasma homocysteine concentrations increased 68% (P< 0.001) in the NA p hase, consistent with chronic increased transmethylation demand. We conclud e that 1) NA acutely and chronically decreases VLDL-TG production rate in n ormal women; 2) the acute effect on VLDL-TG production is associated with a n initial suppression of lipolysis but persists for several hours after the antilipolytic action of NA has abated and is observed in the basal postabs orptive state, when lipolytic rates are not reduced; and 3) the effect of N A on VLDL-TG production, therefore, cannot be completely explained by its a ntilipolytic actions.