Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia

Malmendier, Claude; Delcroix, Claude

doi:10.1016/0021-9150(85)90095-4

Cited by 82 publications

(26 citation statements)

References 20 publications

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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: 76%

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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Section: Hdl Kinetics In Humans Administered Pharmacotherapiesmentioning

confidence: 76%

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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“…There is some confusion in this area that stems from differences between human and rodent apoA-I gene regulation by fibrates. In rats, serum HDL cholesterol and hepatic apoA-I mRNA levels are typically down-regulated by fibrates (20,26,28), whereas these parameters increase to a variable extent in humans (26,29,30). The mechanisms by which fibrates exert an overall negative effect on the minimal promoter of the mouse apoA-I gene are as of yet not defined.The present results, which demonstrate an increase in liver apoA-I mRNA levels under basal conditions in PPAR␣ (Ϫ/Ϫ) mice and show no regulatory effect of fibrates in these mice, are consistent with a negative regulatory effect of PPAR activators on rodent apoA-I expression (20,26).…”

Section: Discussionmentioning

confidence: 99%

Alterations in Lipoprotein Metabolism in Peroxisome Proliferator-activated Receptor α-deficient Mice

Peters

Hennuyer

Staels

et al. 1997

Journal of Biological Chemistry

405

279

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The peroxisome proliferator-activated receptor-␣ (PPAR␣) controls gene expression in response to a diverse class of compounds collectively referred to as peroxisome proliferators. Whereas most known peroxisome proliferators are of exogenous origin and include hypolipidemic drugs and other industrial chemicals, several endogenous PPAR␣ activators have been identified such as fatty acids and steroids. The latter finding and the fact that PPAR␣ modulates target genes encoding enzymes involved in lipid metabolism suggest a role for PPAR␣ in lipid metabolism. This was investigated in the PPAR␣-deficient mouse model. Basal levels of total serum cholesterol, high density lipoprotein cholesterol, hepatic apolipoprotein A-I mRNA, and serum apolipoprotein A-I in PPAR␣-deficient mice are significantly higher compared with wild-type controls. Treatment with the fibrate Wy 14,643 decreased apoA-I serum levels and hepatic mRNA levels in wild-type mice, whereas no effect was detected in the PPAR␣-deficient mice. Administration of the fibrate Wy 14,643 to wild-type mice results in marked depression of hepatic apolipoprotein C-III mRNA and serum triglycerides compared with untreated controls. In contrast, PPAR␣-deficient mice were unaffected by Wy 14,643 treatment. These studies demonstrate that PPAR␣ modulates basal levels of serum cholesterol, in particular high density lipoprotein cholesterol, and establish that fibrate-induced modulation in hepatic apolipoprotein A-I, C-III mRNA, and serum triglycerides observed in wild-type mice is mediated by PPAR␣.

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“…The same group later showed that fenofibrate increases the catabolism of VLDL 1 , reducing its conversion of VLDL 2, and also accelerates the production and catabolism of LDL 2 , consistent with a distribution of LDL particles to a larger less dense type (43). Fibrates have also been demonstrated to increase the synthesis of apoAI in familial hyperlipidemias (44,45), but not all reports have been consistent.…”

Section: Regulation Of Apoai and Apob-100 Kineticsmentioning

confidence: 92%

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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Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia

Cited by 82 publications

References 20 publications

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

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

Alterations in Lipoprotein Metabolism in Peroxisome Proliferator-activated Receptor α-deficient Mice

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

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