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Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome.
Arterioscler Thromb Vasc Biol. 2008 Oct; 28(10):1831-7.AT

Abstract

OBJECTIVE

The metabolic syndrome (MetS) is characterized by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood.

METHODS AND RESULTS

The effects of atorvastatin (40 mg/d) and fenofibrate (200 mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a crossover trial of 11 MetS men. VLDL-apoC-III kinetics were studied, after intravenous d(3)-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (P<0.001) plasma concentrations of triglyceride, apoB, apoB-48, and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (P<0.05). Both agents significantly increased the fractional catabolic rate (+32% and +30%, respectively) and reduced the production rate of VLDL-apoC-III (-20% and -24%, respectively), accounting for a significant reduction in VLDL-apoC-III concentrations (-41% and -39%, respectively). Total plasma apoC-III production rates were not significantly altered by the 2 agents. Neither treatment altered insulin resistance and body weight.

CONCLUSIONS

Both atorvastatin and fenofibrate have dual regulatory effects on VLDL-apoC-III kinetics in MetS; reduced production and increased fractional catabolism of VLDL-apoC-III may explain the triglyceride-lowering effect of these agents.

Authors+Show Affiliations

Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18566295

Citation

Chan, Dick C., et al. "Atorvastatin and Fenofibrate Have Comparable Effects On VLDL-apolipoprotein C-III Kinetics in Men With the Metabolic Syndrome." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 10, 2008, pp. 1831-7.
Chan DC, Watts GF, Ooi EM, et al. Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28(10):1831-7.
Chan, D. C., Watts, G. F., Ooi, E. M., Ji, J., Johnson, A. G., & Barrett, P. H. (2008). Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(10), 1831-7. https://doi.org/10.1161/ATVBAHA.108.170530
Chan DC, et al. Atorvastatin and Fenofibrate Have Comparable Effects On VLDL-apolipoprotein C-III Kinetics in Men With the Metabolic Syndrome. Arterioscler Thromb Vasc Biol. 2008;28(10):1831-7. PubMed PMID: 18566295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome. AU - Chan,Dick C, AU - Watts,Gerald F, AU - Ooi,Esther M M, AU - Ji,Juying, AU - Johnson,Anthony G, AU - Barrett,P Hugh R, Y1 - 2008/06/19/ PY - 2008/6/21/pubmed PY - 2008/10/10/medline PY - 2008/6/21/entrez SP - 1831 EP - 7 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 28 IS - 10 N2 - OBJECTIVE: The metabolic syndrome (MetS) is characterized by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood. METHODS AND RESULTS: The effects of atorvastatin (40 mg/d) and fenofibrate (200 mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a crossover trial of 11 MetS men. VLDL-apoC-III kinetics were studied, after intravenous d(3)-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (P<0.001) plasma concentrations of triglyceride, apoB, apoB-48, and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (P<0.05). Both agents significantly increased the fractional catabolic rate (+32% and +30%, respectively) and reduced the production rate of VLDL-apoC-III (-20% and -24%, respectively), accounting for a significant reduction in VLDL-apoC-III concentrations (-41% and -39%, respectively). Total plasma apoC-III production rates were not significantly altered by the 2 agents. Neither treatment altered insulin resistance and body weight. CONCLUSIONS: Both atorvastatin and fenofibrate have dual regulatory effects on VLDL-apoC-III kinetics in MetS; reduced production and increased fractional catabolism of VLDL-apoC-III may explain the triglyceride-lowering effect of these agents. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/18566295/Atorvastatin_and_fenofibrate_have_comparable_effects_on_VLDL_apolipoprotein_C_III_kinetics_in_men_with_the_metabolic_syndrome_ L2 - https://www.ahajournals.org/doi/10.1161/ATVBAHA.108.170530?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -