Differential Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome
Abstract
The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d3-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL2 cholesterol (P < 0.001), HDL3 cholesterol (P < 0.01), apoAI (P = 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.
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The findings regarding the effect of PPARα agonism on hepatic VLDL cholesterol apolipoprotein B levels and triglyceride production are less consistent than those regarding increases in lipoprotein lipase activity.
“although the findings regarding the latter effect of PPARα agonism are less consistent than those regarding increases in the activity of lipoprotein lipase. 17-19”
From Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk (2022) · cites this paper as [18]
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References 54 · Cited by 219
- Authors
- Watts, G. F., Barrett, P. H. R., Ji, J., Serone, A. P., Chan, D. C., Croft, K. D., Loehrer, F., & Johnson, A. G.
- Affiliations
- The University of Western Australia (AU)
- Prince of Wales Hospital (AU)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-03-01
- Volume
- 52
- Issue
- 3
- Pages
- 803-811
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2169911638
- Cited by
- 219
- References
- 54
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 13 · 2013: 17 · 2012: 10
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- National Institutes of Health (5p41rr012609-03)
- National Center for Research Resources (RR12609)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- metabolic syndrome, atorvastatin, fenofibrate, apolipoprotein A-I, apolipoprotein B, lipoprotein kinetics, fractional catabolic rate, apolipoprotein C-III, cholesteryl ester transfer protein, dyslipidemia, insulin resistance, combination lipid-lowering therapy, HDL cholesterol, triglycerides, atherosclerosis
- MeSH terms
- Atorvastatin, Adult, Hypolipidemic Agents, Apolipoproteins B, Blood Glucose, Cholesterol, Diet, Double-Blind Method, Heptanoic Acids, Humans, Insulin, Kinetics, Lipoproteins, Lipoproteins, HDL, Cholesterol, HDL, Lipoproteins, LDL, Cholesterol, LDL, Lipoproteins, VLDL, Male, Middle Aged, Obesity, Placebos, Fenofibrate, Pyrroles, Triglycerides, Apolipoprotein A-I, Cross-Over Studies, Metabolic Syndrome, Apolipoprotein B-100, Lipoproteins, IDL
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