A novel ELISA system demonstrates that fasting serum apoB-48 levels correlate with triglycerides and are markedly elevated in specific hyperlipidemias, serving as a useful parameter for evaluating exogenous lipoprotein metabolism.
The present study was designed to evaluate the metabolism of chylomicron and chylomicron remnants by measuring serum apolipoprotein B-48 (apoB-48) levels in 335 normolipidemic and 253 hyperlipidemic subjects using a novel ELISA system. The distribution of fasting serum apoB-48 levels in normolipidemic subjects varied widely, ranging from 24 μg/ml (mean, 5.2 ± 3.8 μg/ml; median, 3.9 μg/ml). Serum apoB-48 levels correlated with serum triglyceride (TG) concentrations (r = 0.45, P 24 μg/ml (mean, 5.2 ± 3.8 μg/ml; median, 3.9 μg/ml). Serum apoB-48 levels correlated with serum triglyceride (TG) concentrations (r = 0.45, P 500 mg/dl. Two patients with lipoprotein lipase (LPL) deficiency (Type I hyperlipidemia), five patients with familial dysbetalipoproteinemia (Type III hyperlipidemia), and seven Type V hyperlipidemic patients who were referred to Osaka University Hospital for the examination of hyperlipidemia were also added to the hyperlipidemic group, because the original hyperlipidemic group contained no Type I, no Type III, and only one subject with Type V hyperlipidemia. LPL deficiency was determined by measuring LPL activity in postheparin plasma 15 min after injection of sodium heparin (50 IU/kg dysbetalipoproteinemia was based on the presence of hypercholesterolemia and an and the presence of a on of serum lipoproteins. The and of 253 hyperlipidemic and 335 normolipidemic subjects are shown in of 335 normolipidemic subjects and of five familial subjects to in study for evaluation by oral fat subjects their to in this of hyperlipidemic and normolipidemic subjects ± ± 24 μg/ml mg/dl). The level in this group was 5.2 ± 3.8 the was 3.9 and the range for subjects was the between serum apoB-48 levels and and TG serum apoB-48 levels were against serum TG concentrations in 335 normolipidemic subjects. Serum apoB-48 levels correlated with serum TG levels (r = 0.45, P < 0.001), but was no between serum apoB-48 and levels. In to the of measuring serum apoB-48 levels in the evaluation of lipoprotein the fasting serum apoB-48 levels in patients with various of hyperlipidemia were determined to the apoB-48 levels were seven to 18 times higher in the subjects with Type I and and the patients with Type V ± hyperlipidemia, with with familial dysbetalipoproteinemia also levels of serum apoB-48 ± = that chylomicron remnants in The apoB-48 levels in Type IIa ± 3.8 = Type IIb ± = and Type IV ± = hyperlipidemic subjects were higher than the but increase was in with the The ratio of serum apoB-48 levels to serum TG concentrations was calculated in subjects with various forms of hyperlipidemia and in normolipidemic subjects, and is shown in the apoB-48/TG ratio was within the range in Type I and Type V hyperlipidemic subjects, it was in patients with dysbetalipoproteinemia ± P < The apoB-48/TG ratio was more than in five subjects. In to the fasting apoB-48 levels lipoprotein metabolism in exogenous the oral fat loading was in normolipidemic and familial subjects. the serum TG level apoB-48 level and apoB-48/TG ratio in normolipidemic or subjects at the In normolipidemic subjects, serum apoB-48 levels to about with the peak at 3–4 h after oral fat then returned to the baseline level within 6 h. In the group, the fasting levels of apoB-48 were ± and the postprandial peak levels were ± The serum apoB-48 levels to postprandial TG to a apoB-48/TG The fasting and postprandial serum TG levels in subjects with familial dysbetalipoproteinemia were higher at with a to of normolipidemic subjects. The postprandial apoB-48 levels in subjects at levels and to be and the apoB-48/TG after oral fat Several have reported a wide range of fasting apoB-48 levels from μg/ml to μg/ml (11Lemieux S. Fontani R. Uffelman K.D. Lewis G.F. Steiner G. Apolipoprotein B-48 and retinyl palmitate are not equivalent markers of postprandial intestinal lipoproteins.J. Lipid Res. 1998; 39: 1964-1971Google Scholar, 12Schneeman B.O. Kotite L. Todd K.M. Havel R.J. Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans.Proc. Natl. Acad. Sci. USA. 1993; 90: 2069-2073Google Scholar, 13Karpe F. Hamsten A. Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE.J. Lipid Res. 1994; 35: 1311-1317Google Scholar, 14Lovegrove J.A. Isherwood S.G. Jackson K.G. Williams C.M. Gould B.J. Quantitation of apolipoprotein B-48 in triacylglycerol-rich lipoproteins by a specific enzyme-linked immunosorbent assay.Biochim. Biophys. Acta. 1996; 1301: 221-229Google Scholar, 15Smith D. Proctor S.D. Mamo J.C.L.A. Highly sensitive assay for quantitation of apolipoprotein B-48 using an antibody to human apolipoprotein B and enhanced chemiluminescence.Ann. Clin. Biochem. 1997; 34: 185-189Google Scholar, 16Smith D. Watts G.F. Dane-Stewart C. Mamo J.C.L. Post-prandial chylomicron response may be predicted by a single measurement of plasma apolipoprotein B48 in the fasting state.Eur. J. Clin. Invest. 1999; 29: 204-209Google Scholar, 17Lorec A.M. Juhel C. Pafumi Y. Portugal H. Pauli A.M. Lairon D. Defoort C. Determination of apolipoprotein B-48 in plasma by a competitive ELISA.Clin. Chem. 2000; 46: 1638-1642Google Scholar), within which our ± 3.8 also The wide range from the lack of a method of measurement and the of the results as either TRL apoB-48 or plasma apoB-48. the the ELISA system with monoclonal antibodies is to values the time-consuming of In the normolipidemic subjects with fasting serum apoB-48 levels, we not of apoB-48 on the subjects because the were and of and to a h may the fasting levels of studies are to the of levels of fasting serum apoB-48 in subjects. We that the fasting serum apoB-48 concentrations the impaired of chylomicron and/or chylomicron remnants from the hyperlipidemia), and this is by the of Smith D. Watts G.F. Dane-Stewart C. Mamo J.C.L. Post-prandial chylomicron response may be predicted by a single measurement of plasma apolipoprotein B48 in the fasting state.Eur. J. Clin. Invest. 1999; 29: 204-209Google Scholar), a relationship between fasting plasma concentrations of apoB-48 and postprandial kinetics of retinyl and the relation of postprandial hyperlipidemia and the presence or development of is it be also to fasting serum apoB-48 level is also to the of The serum apoB-48 levels in patients with dysbetalipoproteinemia who do not have levels of chylomicrons of atherogenic chylomicron The apoB-48/TG ratio the of dysbetalipoproteinemia from Type I and Type V hyperlipidemia. one chylomicron particle only one of serum apoB-48 concentrations the number of chylomicrons and chylomicron remnant The serum apoB-48 levels and apoB-48/TG ratio in patients with dysbetalipoproteinemia indicate an number of smaller while the apoB-48 levels and low apoB-48/TG ratio in Type I and Type V hyperlipidemia both an number of the particles and of the particles with These results are with elevated levels of chylomicrons in Type I and Type V hyperlipidemia and of chylomicron remnants in is to dysbetalipoproteinemia from Type IIb or Type V hyperlipidemia based on serum levels familial dysbetalipoproteinemia is a very atherogenic patients with this be more with to and other to against or to the development of atherosclerotic this accurate of this of hyperlipidemia is A of methods for the of dysbetalipoproteinemia have been proposed to the time-consuming and of These a total TG ratio of and particle total TG ratio of both of which the of TRL in a of and the is reported to be more sensitive T. J. Havel R.J. of to serum total is an to and methods in the of familial III Chem. 1999; Scholar). cholesterol is to a of cholesterol in lipoproteins and of a of with and Thus, serum apoB-48 levels and the apoB-48/TG ratio in with serum concentrations also provide an accurate and of with Type IIa, Type IIb, and Type IV hyperlipidemia only a increase in serum apoB-48 levels, elevated TG however, it is that several subjects with Type IV hyperlipidemia almost the levels of apoB-48 as with Type V hyperlipidemia not The results indicate of metabolism in the exogenous and of chylomicrons and/or chylomicron remnants in subjects. In this Type IV hyperlipidemic subjects with elevated apoB-48 levels be as Type V hyperlipidemic they have serum levels. Thus, this the of the of based on serum and TG levels, with to patients with The of apoB-48 response after oral fat loading that of TG response in normolipidemic subjects, that serum apoB-48 concentrations closely exogenous lipoprotein metabolism in the postprandial The peak serum apoB-48 levels and the level of 3–4 h after fat loading are almost in with reported by other (11Lemieux S. Fontani R. Uffelman K.D. Lewis G.F. Steiner G. Apolipoprotein B-48 and retinyl palmitate are not equivalent markers of postprandial intestinal lipoproteins.J. Lipid Res. 1998; 39: 1964-1971Google Scholar, 12Schneeman B.O. Kotite L. Todd K.M. Havel R.J. Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans.Proc. Natl. Acad. Sci. USA. 1993; 90: 2069-2073Google Scholar, 13Karpe F. Hamsten A. Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE.J. Lipid Res. 1994; 35: 1311-1317Google Scholar, 14Lovegrove J.A. Isherwood S.G. Jackson K.G. Williams C.M. Gould B.J. Quantitation of apolipoprotein B-48 in triacylglycerol-rich lipoproteins by a specific enzyme-linked immunosorbent assay.Biochim. Biophys. Acta. 1996; 1301: 221-229Google Scholar, 15Smith D. Proctor S.D. Mamo J.C.L.A. Highly sensitive assay for quantitation of apolipoprotein B-48 using an antibody to human apolipoprotein B and enhanced chemiluminescence.Ann. Clin. Biochem. 1997; 34: 185-189Google Scholar, 16Smith D. Watts G.F. Dane-Stewart C. Mamo J.C.L. Post-prandial chylomicron response may be predicted by a single measurement of plasma apolipoprotein B48 in the fasting state.Eur. J. Clin. Invest. 1999; 29: 204-209Google Scholar, 17Lorec A.M. Juhel C. Pafumi Y. Portugal H. Pauli A.M. Lairon D. Defoort C. Determination of apolipoprotein B-48 in plasma by a competitive ELISA.Clin. Chem. 2000; 46: 1638-1642Google Scholar, S.D. of apoB-48 and apoB-100 triglyceride-rich lipoproteins to postprandial in the plasma concentration of TRL and retinyl Lipid Res. 1993; 34: Scholar). On the other hand, serum apoB-48 levels in subjects did not serum TG concentrations that a increase and in the postprandial The change of TG and apoB-48 levels in dysbetalipoproteinemia was by a continuous in the apoB-48/TG ratio after the fat with the response of apoB-48 in normolipidemic subjects, the levels of serum apoB-48 after fat loading in dysbetalipoproteinemia is of The lack of increase in apoB-48 levels after fat loading may only the of a increase by the very fasting levels. the continuous of the apoB-48/TG ratio the that the TG levels after fat loading in dysbetalipoproteinemia are more to of lipoprotein particles with TG than to particle numbers. The of the between subjects with and dysbetalipoproteinemia in response of apoB-48 and TG after fat loading In in the present study we a novel ELISA system for measurement of serum apoB-48 and the of measurement for the evaluation of lipoprotein metabolism in exogenous pathways. Serum apoB-48 level may become a for the of postprandial hyperlipidemia, one of the risk for coronary studies are to the relationship between serum apoB-48 levels and atherosclerotic cardiovascular The to and for their was by a for Research and to from the Ministry of and in coronary heart disease of lipoprotein lipase particle retinyl palmitate total cholesterol triglyceride TG-rich lipoprotein
Sakai et al. (Sun,) studied this question.