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(Circulation. 1998;98:2088-2093.)
© 1998 American Heart Association, Inc.

Cardiovascular Drugs

Mechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism

Bart Staels, PhD; Jean Dallongeville, MD, PhD; Johan Auwerx, MD, PhD; Kristina Schoonjans, PhD; Eran Leitersdorf, MD; ; Jean-Charles Fruchart, PhD

From Unité 325 INSERM (B.S., J.D., J.A., K.S., J.-C.F.), Département d'Athérosclérose, Institut Pasteur de Lille, 59019 Lille, France, and Center for Research, Prevention and Treatment of Atherosclerosis (E.L.), Division of Medicine, Hadassah University Hospital, 91120 Jerusalem, Israel.

Correspondence to Jean-Charles Fruchart, Département d'Athérosclérose et INSERM U325, Institut Pasteur de Lille, 1, rue du Prof. Calmette, 59019 Lille Cédex, France. E-mail Jean-Charles.Fruchart{at}pasteur-lille.fr

Abstract

Abstract—Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations. Recent investigations indicate that the effects of fibrates are mediated, at least in part, through alterations in transcription of genes encoding for proteins that control lipoprotein metabolism. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-{alpha} form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase—mediated lipolysis via PPAR. Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the ß-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production. In summary, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.


Key Words: apolipoproteins • arteriosclerosis • fibrates • hypercholesterolemia • hyperlipoproteinemia • lipids • PPAR

A vast number of studies confirmed the intimate and causative relationships between dyslipidemias and coronary heart disease. Although hypercholesterolemia is an important underlying cause for coronary heart disease, other dyslipidemias, such as hypoalphalipoproteinemia (low plasma HDL) and hypertriglyceridemia, may be causative in a substantial number of cases. Fibrates are useful for the treatment of hypoalphalipoproteinemia with or without hypertriglyceridemia.1 2 The recommendation for the use of fibrates in certain types of dyslipidemia has gained additional support from a subgroup analysis of the Helsinki Heart Study,3 which showed that the best preventive efficacy has been achieved in a subset of {approx}10% of the study population who had a baseline LDL:HDL cholesterol ratio of >5 and a triglyceride level of 2.3 mmol/L.4 5 Results from angiographic trials revealed that fibrates retard the progression of coronary atherosclerosis and decrease the number of coronary events.6 7

Pharmacological Action of Fibrates

Fibrates are generally effective in lowering elevated plasma triglycerides and cholesterol. The magnitude of lipid changes depends, however, on the patient's pretreatment lipoprotein status8 as well as the relative potency of the fibrate used.9 The most pronounced effects of fibrates are a decrease in plasma triglyceride-rich lipoproteins (TRLs). Levels of LDL cholesterol (LDL-C) generally decrease in individuals with elevated baseline plasma concentrations, and HDL cholesterol (HDL-C) levels are usually increased when baseline plasma concentrations are low.8 However, paradoxical increases in LDL-C have been reported in some patients with dyslipidemia.10 Fibrate treatment results in a reduction of the LDL fraction of atherogenic small, dense particles with an equivalent increase in the intermediate subfraction.11 12 13 Within the triglyceride-rich apolipoprotein (apo) B-containing lipoproteins, fibrates efficiently reduce the apoC-III–containing particles,14 15 which are markers for increased risk for atherogenesis.16 The increased HDL concentrations after fibrates are generally reflected by increased plasma levels of apoA-I and apoA-II,14 15 a change that is associated with an increase in lipoprotein (Lp) A-I:A-II, and a decrease in LpA-I concentrations in patients treated with fenofibrate.14 15

Mechanisms of Action of Fibrates
Evidence from studies in rodents and in humans is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:

1. Induction of lipoprotein lipolysis. Increased TRL lipolysis could be a reflection of changes in intrinsic lipoprotein lipase (LPL) activity17 or increased accessibility of TRLs for lipolysis by LPL owing to a reduction of TRL apoC-III content.18

2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production. In rodents, fibrates increase FA uptake and conversion to acyl-CoA by the liver owing to the induction of FA transporter protein (FATP)19 and acyl-CoA synthetase (ACS) activity.20 Induction of the ß-oxidation pathway with a concomitant decrease in FA synthesis by fibrates results in a lower availability of FAs for triglyceride synthesis, a process that is amplified by the inhibition of hormone-sensitive lipase in adipose tissue by fibrates.21

3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which are thus catabolized more rapidly.11

4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.22

5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in liver,23 24 which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

Role of Transcription Factors in Mediating Fibrate Action

It has been known for several years that fibrates induce peroxisome proliferation in rodents.25 26 This process is linked to the induction of transcription of genes involved in peroxisomal ß-oxidation and is mediated by specific transcription factors, therefore termed peroxisome proliferator-activated receptors (PPARs).

The PPAR Family of Transcription Factors
PPARs are members of the superfamily of nuclear hormone receptors, which are transcription factors transmitting signals that originate from lipid-soluble factors (eg, hormones, vitamins, and FAs) to the genome.25 26 Nuclear receptors recognize and bind to DNA at specific sites, called response elements (REs), which consist of derivatives of the AGGTCA sequence. During evolution, mutation, duplication, and addition of flanking sequences have generated REs distinctive for the various receptors. Once bound to its RE, the receptor complex can activate or repress the expression of a target gene.

PPARs heterodimerize with the retinoid X receptor (RXR) and bind to REs arranged as direct repeats spaced by 1 nucleotide (DR1), termed peroxisome proliferator response elements (PPREs) (FigureDown). To date, 3 different PPAR genes ({alpha}, {delta} [also termed ß, NUC I, or FAAR], and {gamma}) have been identified.25 PPARs display distinct expression patterns, which suggests important functional differences. PPAR-{alpha} is predominantly expressed in tissues that metabolize high amounts of FAs, such as liver, kidney, heart, and muscle.27 The expression of PPAR-{gamma} is high in adipose tissue, where it triggers adipocyte differentiation and induces the expression of genes critical for adipogenesis.26



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  		Figure 1. The PPAR signaling pathway and its natural and synthetic activators. After activation by its respective ligands, PPARs heterodimerize with the receptor for 9cis-retinoic acid (9cRA), RXR, and bind to specific REs in the regulatory regions of target genes, termed PPREs, which are composed of 2 degenerate hexanucleotide repeats (arrows) arranged in tandem as direct repeats spaced by 1 nucleotide.

FAs and derivatives, such as prostaglandin J2 for PPAR-{gamma}28 29 or 8(S)hydroxyeicosatetraenoic acid,30 31 8(S)hydroxyeicosapentaenoic acid,31 and leukotriene B432 for PPAR-{alpha}, have been implicated as natural PPAR ligands. Fibrates are synthetic ligands for PPAR-{alpha}.30 31 32

In rodents, fibrates induce the expression of genes involved in intracellular FA metabolism, such as peroxisomal and mitochondrial ß-oxidation, {omega}-hydroxylation, and ketogenesis.33 By contrast, very few data are available on the regulation of their human counterparts, and it awaits further study to determine whether fibrates and/or PPARs also regulate the expression of any of these genes in humans. However, in contrast to rodents, there is no evidence that fibrates would induce peroxisome proliferation in humans and primates.34

The Role of PPARs in Mediating Fibrate Action on Lipoprotein Metabolism in Humans
TRL Metabolism
The hypotriglyceridemic action of fibrates involves combined effects on LPL17 and apoC-III expression,34 resulting in increased lipolysis. The induction of LPL expression occurs at the transcriptional level and is mediated by PPAR. The latter binds to a PPRE that is present both in the human and the mouse LPL gene promoters.35

In contrast to LPL, transcription of the apoC-III gene is inhibited by fibrates, resulting in decreased production of apoC-III in the liver.34 The repression of apoC-III gene expression by fibrates is mediated via PPAR-{alpha}.36 Consistent with the repression of apoC-III expression, turnover studies in humans indicate that fibrates reduce apoC-III synthesis,18 leading to enhanced LPL-mediated catabolism of VLDL particles. Moreover, fibrates also decrease apoB and VLDL production.37 As a consequence, a reduced secretion of VLDL particles, together with the enhanced catabolism of triglyceride-rich particles, most likely accounts for the hypolipidemic effect of fibrates.

Animal studies suggest that fibrates also increase the hepatic uptake of free FAs (FFAs) by specific FATPs19 and generation of acyl-CoA esters by ACS.20 Owing to an increased ß-oxidation activity and a reduction in acetyl-CoA carboxylase and FA synthase activities,38 FFA metabolism is shifted from triglyceride synthesis to catabolism. Although fibrates do not induce peroxisomal ß-oxidation in humans, it is conceivable that they also affect FA uptake, conversion, and catabolism through the mitochondrial ß-oxidation pathway in humans.

HDL Metabolism
In humans, fibrates increase plasma levels of HDL and its major constituents, apoA-I and apoA-II, to a variable extent39 40 and stimulate apoA-I production in human apoA-I transgenic mice and human hepatocytes.24 In vitro studies have demonstrated that the induction of human apoA-I gene expression after fibrates may be mediated by the interaction of PPAR with a functional PPRE, localized in the A site of the apoA-I promoter.41 Human apoA-II plasma concentrations increase after fibrate treatment.14 15 This is a consequence of the induction of hepatic apoA-II synthesis by fibrates and is mediated through PPAR/RXR heterodimers.23

Indications and Clinical Use of Fibrates in Specific Lipoprotein Disorders

Primary Hypertriglyceridemia
Fibrates are first-line drugs for the treatment of primary hypertriglyceridemia. In these patients, fibrates most noticeably decrease plasma TRLs42; they also decrease, albeit to a lesser extent, total cholesterol, whereas HDL-C levels increase.42 The reduction in cholesterol and triglycerides is mainly due to a fall in VLDL, which is accompanied by changes in VLDL composition.42 Fibrates predominantly reduce the concentrations of large VLDL subfractions.43 44 In addition, fibrates attenuate the postprandial lipid response in hypertriglyceridemic subjects.44

LDL lipid composition is normalized in hypertriglyceridemic patients, who generally have low levels of LDL with an abnormal lipid composition.45 The cholesteryl ester content of LDL increases in all LDL subclasses, resulting in large, less-dense LDL particles.13 43 These changes lead to increased interactions of LDL particles with the LDL receptor, thereby improving LDL clearance.46

HDL-C levels, which are low in patients with hypertriglyceridemia, increase after treatment with fibrates.42 The lowering of the pool of TRLs on treatment with fibrates results in the reduction of net cholesteryl ester transfer from HDL to TRLs,22 which, in association with unchanged lecithin:cholesterol acyl transferase (LCAT) activity, will ultimately lead to an increase in cholesteryl ester and a decrease in triglyceride content of HDL. Improvement of LPL-mediated lipolysis of TRLs43 and increased apoA-I and apoA-II synthesis may also contribute to the rise in HDL levels on treatment with fibrates by promoting the formation of HDL precursors.

Type III Dysbetalipoproteinemia
Type III dysbetalipoproteinemia is a rare lipid disorder resulting from homozygosity for the rare apoE2 isoform in predisposed subjects. The characteristic disturbance of this metabolic disorder is the accumulation of cholesterol-enriched VLDL, which migrates in ß-position on agarose gel electrophoresis. Fibrates have a spectacular lipid-lowering potential in patients with type III dysbetalipoproteinemia.15 47 48 The levels of circulating triglycerides and cholesterol are greatly diminished. The reduction in cholesterol is accounted for by the major reduction of VLDL cholesterol (VLDL-C) and IDL cholesterol, the most atherogenic lipoproteins in patients with type III dysbetalipoproteinemia. Simultaneously, LDL-C and HDL-C, which are usually low, increase significantly. As a consequence of the reduction in ß-VLDL,15 regression of xanthoma and improvement of manifestations of atherosclerosis are observed 49

Combined Hyperlipidemia
Fibrates efficiently lower plasma cholesterol, VLDL-C, and triglycerides and increase HDL-C in combined hyperlipidemia.50 The reduction in total cholesterol is accounted for by the fall in both VLDL-C and LDL-C,51 whereas the reduction of triglyceride levels is associated with normalization of the typical atherogenic LDL subspecies profile in this lipid disorder. Fibrate treatment reduces the levels of dense LDL and of LDL-triglyceride content. Mean LDL peak particle size may increase to normal or remain small,52 but the mean LDL flotation rate augments because of an increase in buoyant LDL concentration.52

Primary Hypercholesterolemia
Although fibrates are not considered to be first-line drugs in primary hypercholesterolemia,1 2 the new generation of fibrates efficiently reduce plasma cholesterol and LDL-C and increase HDL-C concentrations when used in monotherapy in patients with primary hypercholesterolemia.51 53 However, it should be emphasized that the response of hypercholesterolemic patients to fibrate treatment is heterogenous, and nonresponse or even a paradoxical increase in LDL has been observed.54 55 The reduction in total cholesterol is accounted for by a fall in both VLDL-C and LDL-C.53 Fibrates reduce the dense LDL but not the light LDL fraction,56 57 which is less susceptible to oxidation.13 The affinity of LDL for cellular receptors is not affected by treatment in patients with primary hypercholesterolemia.57 The increase in HDL-C is related to a lower cholesteryl ester transfer protein activity, whereas LCAT activity is not affected.57 In patients with primary hypercholesterolemia, LPL activity also increases on treatment with fibrates, resulting in a reduction of postprandial lipemia.58

Non–Insulin-Dependent Diabetes Mellitus
In non–insulin-dependent diabetes mellitus (NIDDM) with hyperlipemia, fibrates lower plasma cholesterol, triglycerides, VLDL, and IDL.54 59 60 61 The levels of apoC-III decrease, resulting in improvement of TRL lipolysis and clearance.59 62 The effect on LDL-C and apoB is dependent on the concentration of plasma TG.54 60 61 The mean LDL particle diameter increases, whereas the concentration of dense LDL decreases in proportion to the changes in triglycerides.63 Fibrates increase total HDL-C mainly owing to an elevation of the HDL3 fraction.62 As in patients with primary hyperlipemia, fibrates reduce postprandial lipemia in patients with NIDDM.64

Tolerability and Safety

In general, fibrates are considered to be well tolerated, with an excellent safety profile. A low incidence of fibrate-associated toxicity has been reported in almost every organ system.65 In accordance with this notion, a summary of 10 years' experience with fenofibrate with an exposure of 6 million patient-years including 7145 patients involved in clinical trials revealed a low frequency of side effects.66

Members of the 2 most popular classes of lipid-lowering drugs, HMG CoA reductase inhibitors and fibrates, cause cancer in rodents.67 Although the mechanism may be related to peroxisome proliferation, a definite link has not yet been established. In humans, long-term administration of various fibrates does not cause peroxisome proliferation or any other morphological changes in the liver.68 69 Extrapolation of this evidence of carcinogenesis from rodents to humans is uncertain.

Clinically relevant interactions of fibrates with other antihyperlipidemic drugs include rhabdomyolysis (reported in combination with HMG CoA reductase inhibitors) and decreased bioavailability when combined with some bile acid sequestrants. Finally, potentiation of the anticoagulant effect of coumarin derivatives may cause bleeding.70

Future Perspectives
The better understanding of the basic mechanisms of action of fibrates in both rodents and humans should now allow the development of novel compounds on a more rational basis. Because the currently available fibrates (TableDown) are rather nonspecific activators of various PPARs, it is expected that more potent and subtype-specific PPAR ligands and/or activators might constitute a novel class of "superfibrates." These compounds might enhance specificity, reduce side effects, and widen the clinical indications of this class of lipid-lowering drugs. Ongoing large clinical studies should confirm their effectiveness in reducing coronary events and demonstrate a possible benefit on coronary and total mortality.


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  		Table 1. Currently Available Fibrates and Their Pharmacological Characteristics

Acknowledgments

Dr Schoonjans was supported by fellowships from ARC and IFN; Drs Auwerx and Staels are members of the CNRS. This work was supported by INSERM U325, Institut Pasteur De Lille, Région Nord, Pas-de-Calais.

References

  1. Prevention of coronary heart disease: scientific background and new clinical guidelines: recommendations of the European Atherosclerosis Society prepared by International Task Force for Prevention of Coronary Heart Disease. Nutr Metab Cardiovasc Dis. 1992;2:113–156.
  2. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015–3023.[Medline] [Order article via Infotrieve]
  3. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, Mäenpää H, Malkönen M, Mänttäri M, Norola S, Pasternack A, Pikkarainen J, Romo M, Sjoblom T, Nikkilä EA. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317:1237–1245.[Abstract]
  4. Huttunen J, Manninen V, Manttari M, Koskinen P, Romo M, Tenkanen L, Heinonen O, Frick M. The Helsinki Heart Study: central findings and clinical implications. Ann Med. 1991;23:155–159.[Medline] [Order article via Infotrieve]
  5. Huttunen J, Heinonen O, Manninen V, Koskinen P, Hakulinen T, Teppo L, Manttari M, Frick M. The Helsinki heart study: an 8.5-year safety and mortality follow-up. J Intern Med. 1994;235:31–39.[Medline] [Order article via Infotrieve]
  6. Ericsson C-G, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet. 1996;347:849–853.[Medline] [Order article via Infotrieve]
  7. Frick MH, Syvanne M, Nieminen MS, Kauma H, Majahalme S, Virtanen V, Kesaniemi YA, Pasternak A, Taskinen MR. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Circulation. 1997;96:2137–2143.[Abstract/Free Full Text]
  8. Tikkanen M. Fibric acid derivatives. Curr Opin Lipidol. 1992;3:29–33.
  9. Zimetbaum P, Frishman W, Kahn S. Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins. J Clin Pharmacol. 1991;31:25–37.[Abstract]
  10. Davignon J. Fibrates: a review of important issues and recent findings. Can J Cardiol. 1994;10:61B.
  11. Caslake M, Packard C, Gaw E, Murray E, Griffin B, Vallance B, Shepherd J. Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia. Arterioscler Thromb. 1993;13:702–711.[Abstract/Free Full Text]
  12. Bruckert E, Dejager S, Chapman M. Ciprofibrate therapy normalises the atherogenic low-density lipoprotein subspecies profile in combined hyperlipidemia (published erratum appears in Atherosclerosis. 1993 102:129). Atherosclerosis. 1993;100:91–102.[Medline] [Order article via Infotrieve]
  13. de Graaf J, Hendriks J, Demacker P, Stalenhoef A. Identification of multiple dense LDL subfractions with enhanced susceptibility to in vitro oxidation among hypertriglyceridemic subjects: normalization after clofibrate treatment. Arterioscler Thromb. 1993;13:712–719.[Abstract/Free Full Text]
  14. Bard J-M, Parra HJ, Camare R, Luc G, Ziegler O, Dachet C, Bruckert E, Douste-Blazy P, Drouin P, Jacotot B, De Gennes JL, Keller U, Fruchart J-C. A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition. Metabolism. 1992;41:498–503.[Medline] [Order article via Infotrieve]
  15. Lussier-Cacan S, Bard J-M, Boulet L, Nestruck A, Grothé A-M, Fruchart J-C, Davignon J. Lipoprotein composition changes induced by fenofibrate in dysbetalipoproteinemia type III. Atherosclerosis. 1989;78:167–182.[Medline] [Order article via Infotrieve]
  16. Luc G, Fievet C, Arveiler D, Evans A, Bard J, Cambien F, Fruchart J, Ducimetiere P. Apolipoproteins C-III and E in apo-B and non apo B-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. J Lipid Res. 1996;37:508–517.[Abstract]
  17. Heller F, Harvengt C. Effects of clofibrate, bezafibrate, fenofibrate, and probucol on plasma lipolytic enzymes in normolipidaemic subjects. Eur J Clin Pharmacol. 1983;23:57–63.
  18. Malmendier C, Lontie J-F, Delcroix C, Dubois D, Magot T, De Roy L. Apolipoproteins C-II and C-III metabolism in hypertriglyceridemic patients: effect of a drastic triglyceride reduction by combined diet restriction and fenofibrate administration. Atherosclerosis. 1989;77:139–149.[Medline] [Order article via Infotrieve]
  19. Martin G, Schoonjans K, Lefebvre A, Staels B, Auwerx J. Coordinate regulation of the expression of the fatty acid transporter protein (FATP) and acyl CoA synthetase (ACS) genes by PPAR{alpha} and PPAR{gamma} activators. J Biol Chem. 1997;272:28210–28217.[Abstract/Free Full Text]
  20. Schoonjans K, Watanabe M, Suzuki H, Mahfoudi A, Krey G, Wahli W, Grimaldi P, Staels B, Yamamoto T, Auwerx J. Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. J Biol Chem. 1995;270:19269–19276.[Abstract/Free Full Text]
  21. D'Costa MA, Angel A. Inhibition of hormone-stimulated lipolysis by clofibrate: a possible mechanism for its hypolipidemic action. J Clin Invest. 1975;55:138–148.
  22. Mann C, Yen F, Grant A, Bihain B. Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia. J Clin Invest. 1991;88:2059–2066.
  23. Vu-Dac N, Schoonjans K, Kosykh V, Dallongeville J, Fruchart J, Staels B, Auwerx J. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest. 1995;96:741–750.
  24. Berthou L, Duverger N, Emmanuel F, Langouët S, Auwerx J, Guillouzo A, Fruchart J-C, Rubin E, Denèfle P, Staels B, Branellec D. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apo A-I transgenic mice. J Clin Invest. 1996;97:2408–2416.[Medline] [Order article via Infotrieve]
  25. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator activated receptor (PPAR) in mediating effects of fibrates and fatty acids on gene expression. J Lipid Res. 1996;37:907–925.[Abstract]
  26. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta. 1996;1302:93–109.[Medline] [Order article via Infotrieve]
  27. Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Laville M, Staels B, Auwerx J, Vidal H. Tissue distribution and quantification of the expression of the peroxisome proliferator activated receptors and of LXR{alpha} mRNAs in human: effect of obesity and NIDDM in adipose tissue. Diabetes. 1997;46:1319–1327.[Abstract]
  28. Forman B, Tontonoz P, Chen J, Brun R, Spiegelman B, Evans R. 15-Deoxy-{Delta}12,14 prostaglandin J2 is a ligand for the adipocyte determination factor PPAR{gamma}. Cell. 1995;83:803–812.[Medline] [Order article via Infotrieve]
  29. Kliewer S, Lenhard J, Willson T, Patel I, Morris D, Lehman J. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor {gamma} and promotes adipocyte differentiation. Cell. 1995;83:813–819.[Medline] [Order article via Infotrieve]
  30. Kliewer S, Sundseth S, Jones S, Brown P, Wisely G, Koble C, Devchand P, Wahli W, Willson T, Lenhard J, Lehmann J. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A. 1997;94:4318–4323.[Abstract/Free Full Text]
  31. Forman B, Chen J, Evans R. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors {alpha} and {delta}. Proc Natl Acad Sci U S A. 1997;94:4312–4317.[Abstract/Free Full Text]
  32. Devchand P, Keller H, Peters J, Vazquez M, Gonzalez F, Wahli W. The PPAR{alpha}-leukotriene B4 pathway to inflammation control. Nature. 1996;384:39–43.[Medline] [Order article via Infotrieve]
  33. Gulick T, Cresci S, Caira T, Moore D, Kelly D. The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci U S A. 1994;91:11012–11016.[Abstract/Free Full Text]
  34. Staels B, Vu-Dac N, Kosykh V, Saladin R, Fruchart JC, Dallongeville J, Auwerx J. Fibrates down-regulate apolipoprotein C-III expression independent of induction of peroxisomal acyl co-enzyme A oxidase. J Clin Invest. 1995;95:705–712.
  35. Schoonjans K, Peinado-Onsurbe J, Lefebvre A-M, Heyman RA, Briggs M, Deeb S, Staels B, Auwerx J. PPAR{alpha} and PPAR{gamma} activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996;15:5336–5348.[Medline] [Order article via Infotrieve]
  36. Peters JM, Hennuyer N, Staels B, Fruchart J-C, Fievet C, Gonzalez FJ, Auwerx J. Alterations in lipoprotein metabolism in PPAR{alpha}-deficient mice. J Biol Chem. 1997;272:27307–27312.[Abstract/Free Full Text]
  37. Lamb R, Koch J, Bush S. An enzymatic explanation of the differential effects of oleate and gemfibrozil on cultured hepatocyte triacylglycerol and phosphatidylcholine biosynthesis and secretion. Biochim Biophys Acta. 1993;1165:299–305.[Medline] [Order article via Infotrieve]
  38. Maragandakis M, Hankin H. On the mode of action of lipid lowering agents, V: kinetics of the inhibition in vitro of rat acetyl-CoA carboxylase. J Biol Chem. 1971;246:348–354.[Abstract/Free Full Text]
  39. Malmendier C, Delcroix C. Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia. Atherosclerosis. 1985;55:161–169.[Medline] [Order article via Infotrieve]
  40. Mellies M, Stein E, Khoury P, Lamkin G, Glueck C. Effects of fenofibrate on lipids, lipoproteins and apolipoproteins in 33 subjects with primary hypercholesterolaemia. Atherosclerosis. 1987;63:57–64.[Medline] [Order article via Infotrieve]
  41. Vu-Dac N, Schoonjans K, Laine B, Fruchart J, Auwerx J, Staels B. Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem. 1994;269:31012–31018.[Abstract/Free Full Text]
  42. Bradford R, Goldberg A, Schonfeld G, Knopp R. Double-blind comparison of bezafibrate versus placebo in male volunteers with hyperlipoproteinemia. Atherosclerosis. 1992;92:31–40.[Medline] [Order article via Infotrieve]
  43. Dachet C, Cavalerro E, Martin C, Girardot G, Jacotot B. Effect of gemfibrozil on the concentration and composition of very low density and low density lipoprotein subfractions in hypertriglyceridemic patients. Atherosclerosis. 1995;113:1–9.[Medline] [Order article via Infotrieve]
  44. Simo I, Yakichuk J, Ooi T. Effect of gemfibrozil and lovastatin on postprandial lipoprotein clearance in the hypoalphalipoproteinemia and hypertriglyceridemia syndrome. Atherosclerosis. 1993;100:55–64.[Medline] [Order article via Infotrieve]
  45. Bhatnagar D, Durrington P, Mackness M, Arrol S, Winocour P, Prais H. Effects of treatment of hypertriglyceridaemia with gemfibrozil on serum lipoproteins and the transfer of cholesteryl ester from high density lipoproteins to low density lipoproteins. Atherosclerosis. 1992;92:49–57.[Medline] [Order article via Infotrieve]
  46. Nigon F, Lesnik P, Rouis M, Chapman M. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res. 1991;32:1741–1753.[Abstract]
  47. Larsen M, Illingworth D, O'Malley J. Comparative effects of gemfibrozil and clofibrate in type III hyperlipoproteinemia. Atherosclerosis. 1994;106:235–240.[Medline] [Order article via Infotrieve]
  48. Zhao S, Smelt A, Leuven J, Vroom T, van der Laarse A, van't Hooft F. Changes of lipoprotein profile in familial dysbetalipoproteinemia with gemfibrozil. Am J Med. 1994;96:49–56.[Medline] [Order article via Infotrieve]
  49. Zelis R, Amsterdam A, Spann JJ, Mason D. Type IV hyperlipoproteinemia: clofibrate without dietary therapy. JAMA. 1972;222:326–328.[Medline] [Order article via Infotrieve]
  50. Wolf H. Efficacy and tolerability of etofibrate and gemfibrozil in combined hyperlipidaemia. Drug Exp Clin Res. 1994;20:109–113.
  51. Cattin L, Da Col PG, Feruglio FS, Finazzo L, Rimondi S, Descovich G, Manzato E, Zambon S, Crepaldi G, Siepi D, Mannarino E, Ventura A. Efficacy of ciprofibrate in primary type II and IV hyperlipidemia: the Italian multicenter study. Clin Ther. 1990;12:482–488.[Medline] [Order article via Infotrieve]
  52. Hokanson J, Austin M, Zambon A, Brunzell J. Plasma triglyceride and LDL heterogeneity in familial combined hyperlipidemia. Arterioscler Thromb. 1993;13:427–434.[Abstract/Free Full Text]
  53. Lupien P, Brun D, Gagne C, Moorjani S, Bielman P, Julien P. Gemfibrozil therapy in primary type II hyperlipoproteinemia: effects on lipids, lipoproteins and apolipoproteins. Can J Cardiol. 1991;7:27–33.[Medline] [Order article via Infotrieve]
  54. Goldberg R, La-Belle P, Zupkis R, Ronca P. Comparison of the effects of lovastatin and gemfibrozil on lipids and glucose control in non-insulin-dependent diabetes mellitus. Am J Cardiol. 1990;66:16B–21B.[Medline] [Order article via Infotrieve]
  55. Pasternak R, Brown L, Stone P, Silverman D, Gibson C, Sacks F. Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels: a randomized, placebo-controlled trial: Harvard Atherosclerosis Reversibility Project (HARP) Study Group. Ann Intern Med. 1996;125:529–540.[Abstract/Free Full Text]
  56. Tilly-Kiesi M, Tikkanen M. Low density lipoprotein density and composition in hypercholesterolaemic men treated with HMG CoA reductase inhibitors and gemfibrozil. J Intern Med. 1991;229:427–434.[Medline] [Order article via Infotrieve]
  57. Franceschini G, Lovati M, Manzoni C, Michelagnoli S, Pazzucconi F, Gianfranceschi G, Vecchio G, Sirtori C. Effect of gemfibrozil treatment in hypercholesterolemia on low density lipoprotein (LDL) subclass distribution and LDL-cell interaction. Atherosclerosis. 1995;114:61–71.[Medline] [Order article via Infotrieve]
  58. Simpson H, Williamson C, Olivecrona T, Pringle S, Maclean J, Lorimer A, Bonnefous F, Bogaievsky Y, Packard C, Shepherd J. Postprandial lipemia, fenofibrate and coronary artery disease. Atherosclerosis. 1990;85:193–202.[Medline] [Order article via Infotrieve]
  59. Niort G, Cassader M, Gambiano R, Pagano G. Comparison of the effects of bezafibrate and acipimox on the lipid pattern and plasma fibrinogen in hyperlipidaemic type 2 (non-insulin-dependent) diabetic patients. Diabetes Metab. 1992;18:221–228.
  60. Sweany A, Shapiro D, Tate A, Goldberg R, Stein E. Effects of simvastatin versus gemfibrozil on lipids and glucose control in patients with non-insulin-dependent diabetes mellitus: NIDDM Study Group. Clin Ther. 1995;17:186–203.[Medline] [Order article via Infotrieve]
  61. Vuorinen-Markkola H, Yki-Jarvinen H, Taskinen M. Lowering of triglycerides by gemfibrozil affects neither the glucoregulatory nor antilipolytic effect of insulin in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993;36:161–169.[Medline] [Order article via Infotrieve]
  62. Ohrvall M, Lithell H, Johansson J, Vessby B. A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia. Metabolism. 1995;44:212–217.[Medline] [Order article via Infotrieve]
  63. Lahdenpera S, Tilly-Kiesi M, Vuorinen-Markkola H, Kuusi T, Taskinen M. Effects of gemfibrozil on low-density lipoprotein particle size, density distribution, and composition in patients with type II diabetes. Diabetes Care. 1993;16:584–592.[Abstract]
  64. Cavallero E, Piolot A, Jacotot B. Postprandial lipoprotein clearance in type 2 diabetes: fenofibrate effects. Diabetes Metab. 1995;21:118–120.
  65. Sgro C, Escousse A. Side effects of fibrates (except liver and muscle). Therapie. 1991;46:351–354.[Medline] [Order article via Infotrieve]
  66. Roberts W. Safety of fenofibrate: US and worldwide experience. Cardiology. 1989;76:169–179.[Medline] [Order article via Infotrieve]
  67. Newman T, Hulley S. Carcinogenicity of lipid-lowering drugs. JAMA. 1996;275:55–60.[Abstract]
  68. Gariot P, Barrat E, Mejean L, Pointel J, Drouin P, Debry G. Fenofibrate and human liver: lack of proliferation of peroxisomes. Arch Toxicol. 1983;53:151–163.[Medline] [Order article via Infotrieve]
  69. Angelin B, Einarsson K, Leijd B. Effect of ciprofibrate treatment on biliary lipids in patients with hyperlipoproteinemia. Eur J Clin Invest. 1984;14:73–78.[Medline] [Order article via Infotrieve]
  70. Blum A, Seligmann H, Livneh A, Ezra D. Severe gastrointestinal bleeding induced by a probable hydroxycoumarin-bezafibrate interaction. Isr J Med Sci. 1992;28:47–49.[Medline] [Order article via Infotrieve]
  71. Committee of Principal Investigators. A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Br Heart J. 1978;40:1069–1118.[Free Full Text]
  72. Oliver MF, Heady JA, Morris JN, Cooper J. WHO cooperative trial on the primary prevention of ischemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet. 1984;2:600–604.[Medline] [Order article via Infotrieve]
  73. Research Committee of the Scottish Society of Physicians. Ischaemic heart disease: a secondary prevention trial using clofibrate. Br Med J. 1971;4:775–784.
  74. Trial of clofibrate in the treatment of ischaemic heart disease: five year study by a group of physicians of the Newcastle upon Tyne region. Br Med J. 1971;4:767–775.
  75. Tenkanen L, Manttari M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: experience of the Helsinki Heart Study. Circulation. 1995;92:1779–1785.[Abstract/Free Full Text]
  76. Bloomfield Rubins H, Robins SJ, Iwane MK, Boden WE, Elam MB, Fye CL, Gordon DJ, Schaefer EJ, Schectman G, Wittes JT. Rationale and design of the department of veterans affairs high-density lipoprotein cholesterol intervention trial (HIT) for secondary prevention of coronary artery disease in men with low high-density lipoprotein cholesterol and desirable low-density lipoprotein cholesterol. Am J Cardiol. 1993;71:45–52.[Medline] [Order article via Infotrieve]
  77. Goldbourt U, Behar S, Reicher-Reiss H, Agmon J, Kaplinsky E, Graff E, Kishon Y, Caspi A, Weisbort J, Mandelzweig L, Abinader E, Aharon L, Braun S, David D, Flich M, Friedman Y, Kristal N, Leil N, Markiewicz W, Marmor A, Palant A, Pelled B, Rabinowitz B, Reisin L, Roguin N, Rosenfeld T, Schlesinger Z, Sclarovsky S, Sherf L, Tzivoni D, Zahavi I, Zion M, Brunner D. Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial). Am J Cardiol. 1993;71:909–915.[Medline] [Order article via Infotrieve]
  78. Steiner G. The Diabetes Atherosclerosis Intervention Study (DAIS): a study conducted in cooperation with the World Health Organization: the DAIS Project Group. Diabetologia. 1996;39:1655–1661.[Medline] [Order article via Infotrieve]



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