Human Apolipoprotein (Apo) B-48 and ApoB-100 Kinetics With Stable Isotopes

Welty, Francine K.
Lichtenstein, Alice H.
Barrett, P. Hugh R.
Dolnikowski, Gregory G.
Schaefer, Ernst J.

From the Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass, and Population Kinetics, Department of Bioengineering, University of Washington, Seattle (P.H.R.B.).

Received February 5, 1999; revision accepted July 8, 1999.

Correspondence to Francine K. Welty, Division of Cardiology, Beth Israel Deaconess Medical Center, One Autumn Street, 5th Floor, Boston, MA 02215. E-mail [email protected]

Presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 11, 1997, and published in abstract form (Circulation. 1997;96[suppl I]:I-143).

Arteriosclerosis, Thrombosis, & Vascular Biology 19(12):p 2966, December 1999.

The kinetics of apolipoprotein (apo) B-100 and apoB-48 within triglyceride-rich lipoproteins (TRLs) and of apoB-100 within IDL and LDL were examined with a primed-constant infusion of (5,5,5-²H₃) leucine in the fed state (hourly feeding) in 19 subjects after consumption of an average American diet (36% fat). Lipoproteins were isolated by ultracentrifugation and apolipoproteins by SDS gels, and isotope enrichment was assessed by gas chromatography/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. The pool sizes (PS) of TRL apoB-48, VLDL apoB-100, and LDL apoB-100 were 17±10, 273±167, and 3325±1146 mg, respectively. There was a trend toward a faster fractional catabolic rate (FCR) for VLDL apoB-100 than for TRL apoB-48 (6.73±3.48 versus 5.02±2.07 pools/d, respectively, P=0.06). The mean FCRs for IDL and LDL apoB-100 were 10.07±7.28 and 0.27±0.08 pools/d, respectively. The mean production rate (PR) of TRL apoB-48 was 6.5% of VLDL apoB-100 (1.3±0.90 versus 20.06±6.53 mg · kg⁻¹ · d⁻¹, P<0.0001). TRL apoB-48 PS was correlated with apoB-48 PR (r=0.780, P<0.0001) but not FCR (r=−0.1810, P=0.458). VLDL apoB-100 PS was correlated with both PR (r=0.713, P=0.0006) and FCR (r=−0.692, P=0.001) of VLDL apoB-100 and by apoB-48 PR (r=0.728, P=0.0004). LDL apoB-100 PS was correlated with FCR (r=−0.549, P=0.015). These data indicate that (1) the FCRs of TRL apoB-48 and VLDL apoB-100 are similar in the fed state, (2) TRL apoB-48 PS is correlated with TRL apoB-48 PR, (3) VLDL apoB-100 PS is correlated with both PR and FCR of VLDL apoB-100 and PR of TRL apoB-48, and (4) LDL apoB-100 PS is correlated with LDL FCR.