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Am J Physiol Endocrinol Metab 280: E540-E547, 2001;
0193-1849/01 $5.00
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Vol. 280, Issue 3, E540-E547, March 2001

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

Wei Wang1, Alice Basinger1, Richard A. Neese1, Barry Shane1, Su-A Myong1, Mark Christiansen1,2, and Marc K. Hellerstein1,2

1 Department of Nutritional Sciences, University of California, Berkeley, 94720; and 2 Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, California 94110

Our objective was to examine very low density lipoprotein-triglyceride (VLDL-TG) kinetics after chronic and acute administration of nicotinic acid (NA). Incorporation of [1,2,3,4-13C4]palmitate and [2-13C1]glycerol into 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). During posttreatment study, 500 mg of NA were administered acutely at 0800. Under baseline postabsorptive conditions, incorporation curves from 13C-labeled free fatty acid (FFA) and 13C-labeled glycerol were superimposable, and VLDL-TG kinetics were in agreement (t1/2 = 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 concentrations and production rates were lower despite a trend toward elevated plasma FFA concentrations and fluxes. After the acute dose of NA, plasma FFA concentrations 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 phase, consistent with chronic increased transmethylation demand. We conclude that 1) NA acutely and chronically decreases VLDL-TG production rate in normal women; 2) the acute effect on VLDL-TG production is associated with an initial suppression of lipolysis but persists for several hours after the antilipolytic action of NA has abated and is observed in the basal postabsorptive state, when lipolytic rates are not reduced; and 3) the effect of NA on VLDL-TG production, therefore, cannot be completely explained by its antilipolytic actions.

niacin; lipolysis; lipid kinetics; free fatty acids; hepatic triglycerides; stable isotopes


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