Association of N-glycosylation of apolipoprotein B-100 with plasma cholesterol levels in Watanabe heritable hyperlipidemic rabbits.

We have previously demonstrated the heterogeneity of N-linked sugar chains of apolipoprotein (apo) B-100 in Watanabe heritable hyperlipidemic (WHHL) rabbit and fasting Japanese White rabbits (Arteriosclerosis, 10 (1990) 386-393). To investigate further the role of N-linked sugar chains of apo B-100 in lipid metabolism, we examined the correlation between the N-glycosylation of apo B-100 and serum cholesterol levels in WHHL rabbits. The N-linked sugar chains of apo B-100 were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and BioGel P-4 column chromatography. These were found to consist of one neutral (N) and two acidic fractions (A1 and A2). N contained a high mannose type oligosaccharide consisting of Man5.GlcNAc2 to Man9.GlcNAc2, while A1 and A2 contained monosialylated and disialylated complex type oligosaccharides, respectively. The molar ratio varied among the 5 WHHL rabbits. There was an inverse correlation between the ratio of acidic oligosaccharide fractions (A1 + A2) and serum cholesterol levels (r = -0.971, P less than 0.01) in the 5 WHHL rabbits. These results indicate that the N-glycosylation of apo B-100 is closely related to cholesterol metabolism in WHHL rabbits.