A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARα-mediated upregulation of SREBP-2 target genes in the liver.: ThB and cholesterol biosynthesis in the liver
| العنوان: | A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARα-mediated upregulation of SREBP-2 target genes in the liver.: ThB and cholesterol biosynthesis in the liver |
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| المؤلفون: | Marc Espeel, Norbert Latruffe, Marie Charlotte Royer, Grégory Chevillard, Ronald J.A. Wanders, Melina De Bruycker, Valérie Nicolas-Francès, Sander Kersten, Ségolène Arnauld, Anne Athias, Pierre Clouet, Marie Claude Clémencet, Stéphane Mandard, Joseph Gresti, Pascal Degrace, Marco Fidaleo |
| المساهمون: | Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Department of Human Anatomy, Embryology, Histology and Medical Physics, Universiteit Gent = Ghent University [Belgium] (UGENT), Laboratory Genetic Metabolic Diseases, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Universiteit van Amsterdam (UvA), Plateforme Lipidomique [Dijon] (LAP), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Nutrition, Metabolism and Genomics Group, Wageningen University and Research [Wageningen] (WUR), This work was supported by grants from the European Union project 'Peroxisomes' LSHG-CT-2004-512018, the Regional Council of Burgundy and the INSERM U866 center (Dijon). G.C. was supported by a French Ministry of Research and Technology Ph.D. fellowship and M.F. by the Italian 'Ministero della Ricerca Scientifica e Tecnologica'., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Ghent University [Belgium] ( UGENT ), Universiteit van Amsterdam ( UvA ) -Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Plateforme Lipidomique [Dijon] ( LAP ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Wageningen University and Research Centre [Wageningen] ( WUR ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universiteit van Amsterdam (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon) |
| المصدر: | Biochimie Biochimie, Elsevier, 2011, 93 (5), pp.876-91. ⟨10.1016/j.biochi.2011.02.001⟩ Biochimie, 93(5), 876-891. Elsevier Biochimie, Elsevier, 2011, 93 (5), pp.876-91. 〈10.1016/j.biochi.2011.02.001〉 Biochimie, 93(5), 876-891 Biochimie 93 (2011) 5 |
| بيانات النشر: | HAL CCSD, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, MESH: Hepatomegaly, Palmitates, MESH : Pyrimidines, MESH : Gene Deletion, Biochemistry, element-binding proteins, MESH : Acetyl-CoA C-Acyltransferase, Mice, MESH: Up-Regulation, MESH: Animals, MESH : Up-Regulation, MESH: Lipid Metabolism, 0303 health sciences, MESH : Gene Expression Regulation, Thiolase, 030302 biochemistry & molecular biology, General Medicine, MESH : Hepatomegaly, Up-Regulation, zellweger-syndrome, Peroxisome Proliferators, MESH: Peroxisome Proliferators, Hepatomegaly, Sterol Regulatory Element Binding Protein 2, peroxisomal 3-ketoacyl-CoA thiolase B, MESH: Mitochondria, 3-oxoacyl-coa thiolase, Lathosterol, fatty-acid oxidation, rat-liver, MESH: Sterol Regulatory Element Binding Protein 2, 03 medical and health sciences, MESH : Sterol Regulatory Element Binding Protein 2, Humans, PPAR alpha, MESH : Peroxisome Proliferators, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, PPARa, VLAG, MESH : Oxidation-Reduction, Fatty Acid Oxidation, MESH: Humans, Cholesterol, MESH : Humans, cholesterol, Lipid Metabolism, MESH: Peroxisomes, Sterol regulatory element-binding protein, chemistry, MESH: Pyrimidines, Micro-array analysis, Peroxisomal 3-ketoacyl-CoA thiolase B, PPARα and SREBP-2, Wy14,643, Gene Deletion, MESH: Liver, MESH: Oxidation-Reduction, MESH: Signal Transduction, MESH: Mice, Knockout, Voeding, Metabolisme en Genomica, chemistry.chemical_compound, MESH: Cholesterol, MESH : Lipid Metabolism, Wy14, MESH : Palmitates, MESH: PPAR alpha, MESH : Cholesterol, Mice, Knockout, neuronal migration, Peroxisome, Acetyl-CoA C-Acyltransferase, MESH: Gene Expression Regulation, Metabolism and Genomics, Mitochondria, Liver, Metabolisme en Genomica, ACOX1, Nutrition, Metabolism and Genomics, MESH : Mitochondria, Oxidation-Reduction, Signal Transduction, acyl-coa oxidase, cholesterol-synthesis, MESH : Male, MESH : PPAR alpha, Peroxisome Proliferation, Biology, beta-oxidation, Voeding, proliferator-activated receptors, MESH : Mice, Peroxisomes, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, SCP2, Nutrition, MESH : Signal Transduction, MESH : Liver, MESH: Palmitates, MESH: Male, Pyrimidines, MESH: Acetyl-CoA C-Acyltransferase, Gene Expression Regulation, MESH: Gene Deletion, MESH : Mice, Knockout, MESH : Animals, MESH : Peroxisomes |
| الوصف: | International audience; Peroxisomal 3-ketoacyl-CoA thiolase B (Thb) catalyzes the final step in the peroxisomal β-oxidation of straight-chain acyl-CoAs and is under the transcription control of the nuclear hormone receptor PPARα. PPARα binds to and is activated by the synthetic compound Wy14,643 (Wy). Here, we show that the magnitude of Wy-mediated induction of peroxisomal β-oxidation of radiolabeled (1-(14)C) palmitate was significantly reduced in mice deficient for Thb. In contrast, mitochondrial β-oxidation was unaltered in Thb(-/-) mice. Given that Wy-treatment induced Acox1 and MFP-1/-2 activity at a similar level in both genotypes, we concluded that the thiolase step alone was responsible for the reduced peroxisomal β-oxidation of fatty acids. Electron microscopic analysis and cytochemical localization of catalase indicated that peroxisome proliferation in the liver after Wy-treatment was normal in Thb(-/-) mice. Intriguingly, micro-array analysis revealed that mRNA levels of genes encoding cholesterol biosynthesis enzymes were upregulated by Wy in Wild-Type (WT) mice but not in Thb(-/-) mice, which was confirmed at the protein level for the selected genes. The non-induction of genes encoding cholesterol biosynthesis enzymes by Wy in Thb(-/-) mice appeared to be unrelated to defective SREBP-2 or PPARα signaling. No difference was observed in the plasma lathosterol/cholesterol ratio (a marker for de novo cholesterol biosynthesis) between Wy-treated WT and Thb(-/-) mice, suggesting functional compensation. Overall, we conclude that ThA and SCPx/SCP2 thiolases cannot fully compensate for the absence of ThB. In addition, our data indicate that ThB is involved in the regulation of genes encoding cholesterol biosynthesis enzymes in the liver, suggesting that the peroxisome could be a promising candidate for the correction of cholesterol imbalance in dyslipidemia. |
| وصف الملف: | application/octet-stream; application/pdf |
| اللغة: | English |
| تدمد: | 0300-9084 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::327c719edfe9f6e2cc364e14f471e8f1Test https://www.hal.inserm.fr/inserm-00573373Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....327c719edfe9f6e2cc364e14f471e8f1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03009084 |
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