Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.

Shepherd, James; Packard, Chris J.; Stewart, James; Atmeh, Ragheb F.; Clark, Ross; Boag, D E; Carr, Kay; Lorimer, A. R.; Ballantyne, D.; Morgan, Hugh

doi:10.1172/jci111643

Cited by 84 publications

(21 citation statements)

References 48 publications

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“…Only one publication has previously addressed the effect of a statin on HDL turnover (39): the data suggested that pravastatin increased apoAI production, but the study was in normolipidemic subjects and was not placebo controlled. Fibrates have been shown to decrease VLDL apoB production and increase VLDL apoB catabolism in markedly hypertriglyceridemic subjects (40,41). In volunteers with comparable characteris- tics to our population, bezafibrate increased the production and catabolism of LDL apoB (42).…”

Section: Regulation Of Apoai and Apob-100 Kineticssupporting

confidence: 48%

Differential Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome

et al. 2003

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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 d 3 -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 HDL 2 cholesterol (P < 0.001), HDL 3 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. Diabetes 52:803-811, 2003

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Section: Regulation Of Apoai and Apob-100 Kineticssupporting

confidence: 48%

Differential Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome

et al. 2003

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“…The pool size of apoA-I was increased by fenofibrate by inducing a greater increase in apoA-I production rate than its effect on increasing apoA-I FCR. The stimulatory effect of fenofibrate and gemfibrozil on apoA-I production has been confirmed by others (79,85,86), whereas bezafibrate did not significantly alter apoA-I or apoA-II turnover (87). One study (86) demonstrated an increase in FCR with fenofibrate therapy, although the increase in FCR was much less than the increase in production rate.…”

Section: Hdl Kinetics In Humans Administered Pharmacotherapiesmentioning

confidence: 77%

Thematic review series: Patient-Oriented Research. What have we learned about HDL metabolism from kinetics studies in humans?

Rashid

Patterson

Lewis

2006

Journal of Lipid Research

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Plasma measurements of lipids, lipoproteins, and apolipoproteins provide information on the static levels of these fractions without providing key information on the dynamic fluxes of lipoproteins in the circulation. Kinetics studies, in contrast, provide additional information on the production and clearance rates of lipoproteins and the flow of lipids and apolipoproteins through lipoprotein fractions. This information is crucial in accurately delineating the metabolism of HDL in plasma, because plasma concentrations of HDL are the net result of the de novo production and catabolism of HDL as well as the recycling of HDL particles and the contribution to HDL from components of other lipoproteins. Studies aimed at measuring the metabolism of HDL particles have shown that HDL metabolism in vivo is complex and consists of multiple components. Kinetics studies provide a window into the metabolism of HDL, allowing us to better understand the mechanisms of HDL decrease in human conditions and the functionality of HDL particles. Here, we review the progress in our understanding of HDL metabolism derived from in vivo kinetics studies, focusing primarily on studies in humans but also reviewing key studies in animal models.-Rashid, S

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“…Decreased hepatic triglyceride production secondary to the decreased availability of fatty acids and accelerated delipidation and removal of VLDL attributable to enhanced LPL activity have been found to be consistent effects of fibrates in vivo (49)(50)(51). Previous kinetic studies in patients with endogenous hypertriglyceridemia or the metabolic syndrome using either bezafibrate or fenofibrate reported an increase of VLDL apolipoprotein catabolism but no change in VLDL apoB production (37,52).…”

Section: Discussionmentioning

confidence: 93%

Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia

Bilz

Wagner

Schmitz

et al. 2004

Journal of Lipid Research

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Kinetics of apo B and apo AI were assessed in 8 patients with mixed hyperlipidemia at baseline and after 8 weeks of atorvastatin 80 mg q.d. and micronised fenofibrate 200 mg q.d. in a cross-over study. Both increased hepatic production and decreased catabolism of VLDL accounted for elevated cholesterol and triglyceride concentrations at baseline. Atorvastatin significantly decreased triglyceride, total, VLDL and LDL cholesterol and apo B concentrations ( ؊ 65%, ؊ 36%, ؊ 57%, ؊ 40% and ؊ 33%, respectively, P Ͻ 0.05). Kinetic analysis revealed that atorvastatin stimulated the catabolism of apo B containing lipoproteins, enhanced the delipidation of VLDL 1 and decreased VLDL 1 production. Fenofibrate lowered triglycerides and VLDL cholesterol ( ؊ 57% and ؊ 64%, respectively, P Ͻ 0.05) due to enhanced delipidation of VLDL 1 and VLDL 2 and increased VLDL 1 catabolism. Changes of HDL particle composition accounted for the increase of HDL cholesterol during atorvastatin and fenofibrate (18% and 23%, P Ͻ 0.01). Only fenofibrate increased apo AI concentrations through enhanced apo AI synthesis (45%, P Ͻ 0.05). We conclude that atorvastatin exerts additional beneficial effects on the metabolism of apo B containing lipoproteins unrelated to an increase in LDL receptor activity. Fenofibrate but not atorvastatin increases apo AI production and plasma turnover.

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Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.

Cited by 84 publications

References 48 publications

Differential Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome

Differential Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome

Thematic review series: Patient-Oriented Research. What have we learned about HDL metabolism from kinetics studies in humans?

Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia

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