{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:04:33Z","timestamp":1790417073307,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,5,11]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014In humans, fibrates are frequently used normolipidemic drugs. Fibrates act by regulating genes involved in lipoprotein metabolism via activation of the peroxisome proliferator-activated receptor-\u03b1 (PPAR\u03b1) in liver. In rodents, however, fibrates induce a peroxisome proliferation, leading to hepatomegaly and possibly hepatocarcinogenesis. Although this peroxisome proliferative response appears not to occur in humans, it remains controversial whether the beneficial effects of fibrates on lipoprotein metabolism can occur dissociated from such undesirable peroxisomal response. Here, we assessed the influence of fenofibrate on lipoprotein metabolism and peroxisome proliferation in the rabbit, an animal that, contrary to rodents and similar to humans, is less sensitive to peroxisome proliferators.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014First, we demonstrate that in normal rabbits, fenofibrate given at a high dose for 2 weeks does not influence serum concentrations or intestinal mRNA levels of the HDL apolipoprotein apoA-I. Therefore, the study was continued with human apoA-I transgenic rabbits that overexpress the human apoA-I gene under control of its homologous promoter, including its PPAR-response elements. In these animals, fenofibrate increases serum human apoA-I concentrations via an increased expression of the human apoA-I gene in liver. Interestingly, liver weight or mRNA levels and activity of fatty acyl-CoA oxidase, a rate-limiting and marker enzyme of peroxisomal \u03b2-oxidation, remain unchanged after fenofibrate.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Expression of the human apoA-I transgene in rabbit liver suffices to confer fibrate-mediated induction of serum apoA-I. Furthermore, these data provide in vivo evidence that the beneficial effects of fibrates on lipoprotein metabolism occur mechanistically dissociated from any deleterious activity on peroxisome proliferation and possibly hepatocarcinogenesis.\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.18.2445","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"2445-2451","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Beneficial Effects of Fibrates on Apolipoprotein A-I Metabolism Occur Independently of Any Peroxisome Proliferative Response"],"prefix":"10.1161","volume":"99","author":[{"given":"Nathalie","family":"Hennuyer","sequence":"first","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Poulain","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Madsen","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf K.","family":"Berge","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis-Marie","family":"Houdebine","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Branellec","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Fruchart","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Fie\u0301vet","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Duverger","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Staels","sequence":"additional","affiliation":[{"name":"From U325 INSERM, De\u0301partement d\u2019Athe\u0301roscle\u0301rose, Institut Pasteur de Lille and the Faculte\u0301 de Pharmacie, Universite\u0301 de Lille II, France (N.H., P.P., J.C.F., C.F., B.S.); the Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway (L.M., R.K.B.); the Cardiovascular Department, CRVA Rho\u0302ne-Poulenc Rorer-Gencell, Vitry-sur-Seine, France (D.B., N.D.); and INRA, Jouy en Josas, France (L.M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/138161280301221005122647","volume":"3","year":"1997","unstructured":"Staels B, Auwerx J. 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