Introduction: HDL are dysfunctional in hypercholesterolemic patients. We tested the hypothesis that the administration of a vitamin B3 derivative will improve HDL metabolism in a mouse model of hypercholesterolemia.

Materials and methods: Apolipoprotein (Apo)E-deficient (KOE) mice were used. At the age of 8 weeks, KOE mice were challenged with a high-fat diet (containing 0.25% cholesterol, TD88137) for 4 weeks. Groups of five KOE mice were treated with different doses of nicotinamide (NAM) (ie, 0.25% and 1%) via tap water. Untreated KOE mice were used as control group. The ability of HDL to promote both cholesterol efflux in vitro and reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT) was also assessed. Isolated non-HDL lipoproteins were isolated by ultracentrifugation and radiolabeled with [3H]-cholesteryl oleoyl ether and i.v. injected into mice. Plasma and tissue samples were used for chemical analysis, as appropriate.

Results: Compared with untreated mice, the administration of NAM to KOE mice produced a [3H]-cholesterol plasma accumulation ( 1.5-fold; P<0.05) in the m-RCT, while the relative content of [3H]-tracer was reduced in the liver ( 0.7-fold; P=0.10) and feces (> 0.5-fold; P<0.05). Such behavior was accompanied by a significant delay ( 0.8-fold; P<0.05) in the fractional catabolic rate of non-HDL lipoproteins in high-dose, NAM-treated KOE mice, as revealed by kinetic analysis. The latter was mainly explained by an impaired metabolism of non-HDL lipoproteins rather than a damped property by plasma acceptors of cholesterol.
 
Conclusion: Our data show that the administration of NAM to KOE mice impaired plasma non-HDL  lipoprotein clearance and reduced the rate of fecal cholesterol excretion.

04 - EFFECTS OF VITAMIN B3 ON LIPOPROTEIN METABOLISM IN A MOUSE MODEL OF HYPERCHOLESTEROLEMIA