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Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency.
J Clin Invest. 1995 Sep; 96(3):1573-81.JCI

Abstract

The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism. Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels. The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency. We conducted a series of in vivo apo B kinetic studies in tow unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model. The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d). Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls. In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B. This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency.

Authors+Show Affiliations

Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

7657828

Citation

Ikewaki, K, et al. "Increased Catabolic Rate of Low Density Lipoproteins in Humans With Cholesteryl Ester Transfer Protein Deficiency." The Journal of Clinical Investigation, vol. 96, no. 3, 1995, pp. 1573-81.
Ikewaki K, Nishiwaki M, Sakamoto T, et al. Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency. J Clin Invest. 1995;96(3):1573-81.
Ikewaki, K., Nishiwaki, M., Sakamoto, T., Ishikawa, T., Fairwell, T., Zech, L. A., Nagano, M., Nakamura, H., Brewer, H. B., & Rader, D. J. (1995). Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency. The Journal of Clinical Investigation, 96(3), 1573-81.
Ikewaki K, et al. Increased Catabolic Rate of Low Density Lipoproteins in Humans With Cholesteryl Ester Transfer Protein Deficiency. J Clin Invest. 1995;96(3):1573-81. PubMed PMID: 7657828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency. AU - Ikewaki,K, AU - Nishiwaki,M, AU - Sakamoto,T, AU - Ishikawa,T, AU - Fairwell,T, AU - Zech,L A, AU - Nagano,M, AU - Nakamura,H, AU - Brewer,H B,Jr AU - Rader,D J, PY - 1995/9/1/pubmed PY - 2001/3/28/medline PY - 1995/9/1/entrez SP - 1573 EP - 81 JF - The Journal of clinical investigation JO - J Clin Invest VL - 96 IS - 3 N2 - The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism. Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels. The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency. We conducted a series of in vivo apo B kinetic studies in tow unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model. The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d). Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls. In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B. This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/7657828/Increased_catabolic_rate_of_low_density_lipoproteins_in_humans_with_cholesteryl_ester_transfer_protein_deficiency_ L2 - https://doi.org/10.1172/JCI118196 DB - PRIME DP - Unbound Medicine ER -