Submitted to: Metabolism: Clinical and Experimental
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/2/2009
Publication Date: 11/20/2009
Citation: Otokozawa, S., Ai, M., Diffenderfer, M.R., Asztalos, B.F., Tanaka, A., Lamon-Fava, S., Schaefer, E. 2009. Fasting and post-prandial apolipoprotein B-48 levels in healthy, obese, and hyperlipidemic subjects. Metabolism: Clinical and Experimental. 58:1536-1542. Interpretive Summary: With fat feeding there is a significant increase in the levels of fat or triglyceride containing particles in intestine known as chylomicrons, or their remnants. One of the major protein constituents of these intestinal particles, and the only specific marker of intestinal lipoproteins, is apolipoprotein B-48 or apoB-48. We evaluated a new assay for apoB-48 in plasma and triglyceride-rich particles. Reproducibility of the assay was excellent. About 65% of apo B-48 was found in triglyceride-rich particles. In 12 healthy subjects blood apo B-48 levels increased by about 130% in the fed state. In 63 obese subjects, median fasting apo B-48 values were higher than in controls, and fat feeding triglyceride levels increased by about 75% and apoB-48 levels increased by about 100%. In 270 subjects with elevated cholesterol levels, average total apoB values were 100% higher and apoB-48 were 37% higher than in controls. Our data indicates that median apo B-48 values in healthy subjects increase more than 100% in the fed state, and that obese and subjects with elevated cholesterol levels have significantly higher apoB-48 levels in the bloodstream than do controls.
Technical Abstract: Apolipoprotein (apo) B-48 is the only specific marker of intestinal lipoproteins. We evaluated a novel enzyme-linked immunosorbent assay (ELISA) standardized with recombinant apo B-48 to measure apo B-48 in plasma and triglyceride-rich lipoproteins (TRLs, density b1.006 g/mL). Coefficients of variation were less than 2.5%. Assay values correlated well (r = 0.82, P b .001) with values obtained by gel scanning of TRLs (n = 75 samples); however, the gel scanning method yielded values that were about 50% lower than ELISA values. About 60% to 70% of apo B-48 was found in TRLs. In 12 healthy subjects, median fasting plasma apo B-48 levels were 0.51 mg/dL and were increased by 121% to 147% in the fed state. In 63 obese subjects, median fasting apo B-48 values were 0.82 mg/dL; and feeding resulted in almost no change in total cholesterol, non–high-density lipoprotein cholesterol, or total apo B values, whereas triglyceride, remnant lipoprotein cholesterol, and apo B-48 levels were significantly higher (P b .05; by +73%, +58%, and +106%), and direct low-density lipoprotein cholesterol and direct high-density lipoprotein cholesterol were significantly lower (P b .001, by -13% and -20%) than fasting values. Relative to controls, 270 hyperlipidemic subjects had significantly higher (P b .001, +115%) fasting total apo B and higher apo B-48 values (P = .06, +37%). Our data indicates that the apo B-48 ELISA tested provides highly reproducible results and is excellent for research studies. Median apo B-48 values in healthy subjects are about 0.5 mg/dL and increase more than 100% in the fed state. Elevated levels are observed in obese and hyperlipidemic subjects.