DIETARY FISH OIL PLUS LOVASTATIN DECREASES BOTH VLDL AND LDL APO-B PRODUCTION IN MINIATURE PIGS

Our previous apolipoprotein (apo) B kinetic studies of miniature pigs fed fish oil (Maxepa) demonstrated that very low density lipoprotein (VLDL) apo B concentrations were markedly reduced but that low density lipoprotein (LDL) concentrations were only modestly lowered because of a threefold increase in the conversion of VLDL apo B to LDL. In the present study, the effect of Maxepa plus lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on apo B metabolism was assessed. Miniature pigs (n=6) were simultaneously injected with autologous I-131-VLDL and I-125-LDL after a diet of pig chow supplemented with 30 g/day of Maxepa and again after the addition of lovastatin, 30 mg/day. Kinetic data were analyzed by compartmental analysis with use of the CONSAM program. Compared with Maxepa alone, the addition of lovastatin reduced VLDL apo B concentrations by 21% (p<0.003) because of reduced VLDL apo B production (26%, p<0.005), as the fractional clearance rate was not affected. Conversion of VLDL apo B to LDL was reduced by 48% (p<0.005), and the direct removal of VLDL apo B from plasma was reduced by 25% (p<0.01). Maxepa plus lovastatin reduced LDL apo B concentrations by 44% (p<0.004). This was due to a 38% (p<0.002) decrease in LDL production, which was primarily derived from VLDL. The LDL apo B fractional catabolic rate was not significantly changed. Thus, a combination of Maxepa and lovastatin reduces both VLDL and LDL apo B concentrations, primarily by decreasing production rates.